From 3deec8becfa3d7952b85aeaf5b4c1c75cb477526 Mon Sep 17 00:00:00 2001 From: Harriet Dashnow Date: Fri, 15 Mar 2024 21:21:41 -0600 Subject: [PATCH] process files --- data/STR-disease-loci.processed.csv | 142 +++--- data/STR-disease-loci.processed.json | 676 ++++++++++++++++----------- 2 files changed, 477 insertions(+), 341 deletions(-) diff --git a/data/STR-disease-loci.processed.csv b/data/STR-disease-loci.processed.csv index 5369508..9e86ff4 100644 --- a/data/STR-disease-loci.processed.csv +++ b/data/STR-disease-loci.processed.csv @@ -1,73 +1,73 @@ -chrom,start_hg38,stop_hg38,start_hg19,stop_hg19,start_t2t,stop_t2t,notes_t2t,id,disease_id,gene_strand,reference_motif_reference_orientation,pathogenic_motif_reference_orientation,pathogenic_motif_gene_orientation,benign_motif_reference_orientation,benign_motif_gene_orientation,unknown_motif_reference_orientation,unknown_motif_gene_orientation,disease,gene,flank_motif,locus_structure,Inheritance,type,location_in_gene,normal,normal_min,normal_max,intermediate,intermediate_min,intermediate_max,pathogenic,pathogenic_min,pathogenic_max,ref_copies,repeatunitlen,age_onset,age_onset_min,age_onset_max,typ_age_onset_min,typ_age_onset_max,novel,Mechanism,Mechanism_detail,Mechanism_source,source,notes,details,width,OMIM,disease_freq_num,TR-caused_disease_freq,STRipy_gene,gnomAD_gene,GeneReviews,Year -chrX,148500605,148500753,147582125,147582273,146765191,146765342,(GCC)51.3,FRAXE_AFF2,FRAXE,+,GCC,GCC,CCG,,,,,"Fragile X syndrome, FRAXE type",AFF2,,(GCC)*,XR,5' UTR,5’ Region,4-39,4,39,,,,200-2000,200,2000,50.3,3,Typical: 2-10; Range: 1-10 (developmental delays without physical features can make onset difficult to detect until schooling),1,10,2,10,ref,"LOF, reduced gene expression",Loss of function via transcriptional silencing,(doi.org/10.1038/nrg1691) (doi.org/10.1007/s11604-022-01343-5),"Mirkin 2007, OMIM, GeneReviews NBK535148",,,148,309548,"2/50,000","1-4/100,000 males (https://medlineplus.gov/genetics/condition/fragile-xe-syndrome); 1/50-100,000 males, more than 50 families (PMID: 11246464)",AFF2,AFF2,NBK535148,1993 -chr2,100104799,100104824,100721261,100721286,100563686,100563738,(GCC)17.7,FRA2A_AFF3,FRA2A,-,GCC,GCC,CGG,,,,,Intellectual disability associated with fragile site FRA2A,AFF3,,(GCC)*,AD,Intronic,"Intron ",3-20,3,20,,,,300,300,300,8.7,3,Early childhood (small sample size),1,7,1,7,ref,"Decreased gene expression, methylation","""silencing of the FMR2 gene as a consequence of a CCG expansion located upstream of this gene""",malacard,"https://doi.org/10.1038/s41580-021-00382-6, PMC3998887","Path threshold may actually be higher than 300, assay was not sensitive enough",,25,601464,N/A,"1/862 (1/654-1266) population prevalence of methylated AFF3 expansions (mild cognitive disability) +chrom,start_hg38,stop_hg38,start_hg19,stop_hg19,start_t2t,stop_t2t,notes_t2t,id,disease_id,gene_strand,reference_motif_reference_orientation,pathogenic_motif_reference_orientation,pathogenic_motif_gene_orientation,benign_motif_reference_orientation,benign_motif_gene_orientation,unknown_motif_reference_orientation,unknown_motif_gene_orientation,disease,gene,flank_motif,locus_structure,Inheritance,type,location_in_gene,normal,normal_min,normal_max,intermediate,intermediate_min,intermediate_max,pathogenic,pathogenic_min,pathogenic_max,ref_copies,repeatunitlen,age_onset,age_onset_min,age_onset_max,typ_age_onset_min,typ_age_onset_max,novel,Mechanism,Mechanism_detail,Mechanism_source,source,notes,details,width,OMIM,Prevalence,Prevalence_details,STRipy_gene,gnomAD_gene,GeneReviews,Year +chr3,63912685,63912716,63898361,63898392,63956303,63956334,(GCA)10.7,SCA7_ATXN7,SCA7,+,CAG,CAG,AGC,,,,,Spinocerebellar Ataxia Type 7,ATXN7,(CAG)n(CCG)4,(CAG)*(CCG)+,AD,Coding,"Exon 1, 2, or 3 (depending on isoform)",4–19,4,19,28-35,28,35,34–460,34,460,10.7,3,Typical: 4-48 (PMID: 20739808); Range: 0-65 (GeneReview),0,65,4,48,ref,Polyglutamine ,Polyglutamine ,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",,,31,164500,.999/300000,"<1/300,000 (GeneReview)",ATXN7,ATXN7,NBK1256,1996 +chr6,170561907,170562017,170870995,170871105,171935459,171935569,(GCA)37.0,SCA17_TBP,SCA17,+,GCA,GCA,AGC,,,,,Spinocerebellar ataxia type 17,TBP,,(GCA)*,AD,Coding,Exon 3,25–40,25,40,41–48,41,48,49 to 66,49,66,37.0,3,Typical: 19-48; Range: 3-62 [has second variant to delay onset] (OMIM),3,62,19,48,ref,Polyglutamine ,Polyglutamine ,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK1438","Parkinson disease,late-onset",,110,607136,0.2/100000,"Unknown (global), <100 families, 0.47:1,000,000 (Japanese), 0.16/100,000 (England) (GeneReview); Tang et al., 2017: 0.2/100,000",TBP,TBP,NBK1438,1999 +chr19,13207859,13207898,13318673,13318712,13333137,13333176,(CTG)13.3,SCA6_CACNA1A,SCA6,-,CTG,CTG,AGC,,,,,Spinocerebellar Ataxia Type 6,CACNA1A,,(CTG)*,AD,Coding,Last Exon: 47 or 48,4–18,4,18,19,19,19,20–33,20,33,13.3,3,Typical: 43-52 (GeneReview); Range: 16 (PMID: 23331413) - 73 (NBK1140),16,73,43,52,ref,Polyglutamine ,Polyglutamine ,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",,,39,183086,0.3/100000,"13-15% of global SCA prevalence, estimated to be 0.02-31/100,000 (GeneReview); Tang et al., 2017: 0.3-5/100,000",CACNA1A,CACNA1A,NBK1140,1997 +chr3,138946020,138946062,138664862,138664904,141687014,141687051,(GCGGCTGCAGCCGCA)2.5,BPES_FOXL2,BPES,-,NGC,NGC,CNG,,,,,"Blepharophimosis, epicanthus inversus, and ptosis",FOXL2,,(NGC)*,AD,Coding,Exon 1,<14,14,14,,,,>15,15,15,14.0,3,0 (birth),0,0,0,0,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),NBK535148,,,42,110100,0.31/50000,"1 in 50,000 births globally for all BPES, with FOXL2 expansions 31% of pathogenic variants (NBK1441; NBK535148)",FOXL2,FOXL2,NBK535148,2001 +chr13,70139383,70139429,70713515,70713561,69361244,69361271,(CTG)9.3,SCA8_ATXN8OS,SCA8,+,CTG,CTG,CTG,,,,,Spinocerebellar Ataxia Type 8,ATXN8OS,(CTA)10(CTG)n,(CTA)*(CTG)*,AD,3' UTR,Exon 5 or 3’ UTR depending on transcript,15–50,15,50,50-70,50,70,71-1300,71,1300,15.3,3,Typical: 20-40; Range: 0-73 (GeneReview),1,73,20,49,ref,Polyglutamine/toxic gain-of-function; Unknown ,Polyglutamine/toxic gain-of-function; Unknown ,(OMIM) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x","Two genes span the CTG/CAG repeat and are expressed in opposite directions: ATXN8, which encodes a nearly pure polyglutamine expansion protein in the CAG direction, and ATXN8OS (603680), which, when transcribed, produces a noncoding CUG expansion RNA (Moseley et al., 2006). Roda et al. suggested that the ATXN8 or ATXN8OS gene should not be evaluated in isolation as a candidate gene for spinocerebellar degenerative disease",,46,608768,0.5/100000,"<1/100,000; Tang et al., 2017; Expansion in 1:100-1200 chromosomes (GeneReview)",ATXN8OS,ATXN8OS,NBK1268,1999 +chr13,99985448,99985493,100637702,100637747,99196359,99196404,(GCG)15.3,HPE5_ZIC2,HPE5,+,GCN,GCN,CNG,,,,,Holoprosencephaly-5,ZIC2,,(GCN)*,AD,Coding,Exon 3,< 15,15,15,,,,>25,25,25,15.3,3,0,0,0,0,0,ref,Polyalanine ,Polyalanine ,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,45,609637,1.4/1000000,"0.05-0.23/100,000; math done by 40% of pathogenic variants in ZIC2 are expansion (GeneReview); 5% of non-syndromic HPE are ZIC2 gene (NBK1530), and nonsyndromic HPE is [25]-50% of HPE, which affects 1/10,000 newborns (Medline non-syndromic HPE) - ZIC2 is 9.2% of HPE cases, whicho ccur in 1/16,000 live births (PMID: 17274816)",ZIC2,ZIC2,NBK1530,2001 +chr6,16327634,16327724,16327865,16327955,16200189,16200282,(TGC)31.1,SCA1_ATXN1,SCA1,-,CTG,CTG,AGC,,,,,Spinocerebellar Ataxia Type 1,ATXN1,,(CTG)*,AD,Coding,Exon 8,6–35,6,35,36-38,36,38,39–91,39,91,30.3,3,Typical: 20-39 (UptoDate); Range: 6(PMID: 3165612)-63 (PMID: 8825276),6,63,20,39,ref,Polyglutamine,Polyglutamine,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK1184, s40478-021-01201-x",Interruptions: CAT,,90,164400,1.5/100000,"1-2/100,000",ATXN1,ATXN1,NBK1184,1993 +chr12,111598950,111599019,112036754,112036823,111575873,111575940,(GCT)22.3,SCA2_ATXN2,SCA2,-,CTG,CTG,AGC,,,,,Spinocerebellar Ataxia Type 2,ATXN2,,(CTG)*,AD/AR,Coding,Exon 1,14–31,14,31,32-34,32,34,33–200,33,200,23.3,3,Typical: 30-39 (GeneReview); Range: 2-86 (OMIM),2,86,30,39,ref,Polyglutamine ,Polyglutamine ,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, GeneReviews NBK1275, s40478-021-01201-x","29–32 repeats: increased ALS risk, Interruptions: CAA, CGG, CGC. Parkinson disease, late-onset, susceptibility.",,69,183090,1.5/100000,"1-2/100,000 (Tang et al., 2017) (population dependent)",ATXN2,ATXN2,NBK1275,1996 +chr4,3074877,3074940,3076604,3076667,3073604,3073694,(CAG)30.3,HD_HTT,HD,+,CAG,CAG,AGC,,,,,Huntington disease,HTT,(CAG)nCAACAG(CCG)12,(CAG)*CAACAG(CCG)*,AD,Coding,Exon 1,6–26,6,26,"27-35 unstable, 36-39 reduced penetrance",27,39,40–250 (>60 assocated with onset age <20),40,250,21.3,3,Typical: 35-44 (GeneReview); Range: 2-85 (PMID: 21171977),2,85,35,44,ref,Polyglutamine ,Polyglutamine ,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews, PMID: 12791042",CAG exp only pathogenic. Interruptions impact pathogenicity.,,63,143100,1/10000,"Tang et al., 2017: 6.5-15/100,000; 9.71-17:100,000 (European) vs. 0.1-2/100,000 (African), as many as 1 in 400 have reduced penetrance (0.2-2% for 36-38 CAG) HTT alleles (GeneReview)",HTT,HTT,NBK1305,1993 +chr14,23321472,23321502,23790681,23790711,17522488,17522518,,OPMD_PABPN1,OPMD,+,GCN,GCN,CNG,,,,,Oculopharyngeal muscular dystrophy,PABPN1,,(GCN)*,AD/AR,Coding,Exon 1,10,10,10,,,,12-17,12,17,7.0,3,Typical: 40-59 (PMID: 37519616); Range: 20-79 (PMID: 35112761),20,79,40,59,ref,Polyalanine ,Polyalanine ,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Mirkin 2007, GeneReviews NBK1126, s40478-021-01201-x","AR for 11 repeats, AD >12 repeats. Most known patients have (GCG)+, but GCN or any polyalanine may be pathogenic",,20,164300,1/100000,"Tang et al., 2017: 1/100,000; population specific; frequency of GCN[11] alleles is 1-2% of North America/Europe/Japan (GeneReview)",PABPN1,PABPN1,NBK1126,1998 +chr4,41745972,41746032,41747989,41748049,41719745,41719805,(GCC)15.7,CCHS_PHOX2B,CCHS,-,GCN,GCN,CNG,,,,,Congenital central hypoventilation syndrome,PHOX2B,,(GCN)*,AD,Coding,Exon 3,20,15,20,24,24,24,25-33,25,33,15.7,3,Typical: 0-2 (GeneReview/PMID: 15121777); Range: 0-36 (PMID: 16873766),0,36,0,2,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Mirkin 2007, GeneReviews NBK1427, s40478-021-01201-x",ReferenceRegion: 4:41745971-41746032,,46,209880,1/174000,"1:148000-200000 births (Estimated, may include mild/undiagnosed or be overestimate globally) (GeneReview)",PHOX2B,PHOX2B,NBK1427,2003 +chrX,67545317,67545419,66765159,66765261,65975148,65975250,(GCA)33.3,SBMA_AR,SBMA,+,GCA,GCA,AGC,,,,,"Spinal and bulbar muscular atrophy, Kennedy Disease",AR,,(GCA)*,XR,Coding,Exon 1,9–34,9,34,36-37,36,37,38–68,38,68,34.0,3,"Typical: 20-49 (OMIM), Range: 15-75 (https://doi.org/10.1038/sj.ejhg.5200656) ",15,75,20,49,ref,Polyglutamine,Polyglutamine,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",,,102,313200,1/30000,"1-2/100,000 (population-specific, higher in Finnish population, Canadian population) (PMID: 37628685); 1/30,000 (Orphanet) ; mutation frequency of 1:3182 10x more frequent than reported disease prevalence of 1 in 30,000 (PMID: 36797998); Tang et al., 2017: 0.67-2.5/100,000",AR,AR,NBK1333,1991 +chr9,69037286,69037304,71652202,71652220,81210843,81210861,(AAG)9.7,FRDA_FXN,FRDA,+,GAA,GAA,AAG,,,,,Friedreich ataxia,FXN,(A)16(GAA)n,(A)*(GAA)*,AR,Intronic,Intron 1,5–33,5,33,34-65,34,65,66 to 1700,66,1700,6.0,3,Typical: 10-15; Range: 2-80 (GeneReview),2,80,10,15,ref,"LOF, reduced gene expression",Loss of function via transcriptional silencing,(doi.org/10.1038/nrg1691) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148",Not annotated by TRF?,,2,229300,1/50000,"1/50,000 (OMIM); Tang et al., 2017: Known carrier frequency 1000/100,000; observed 421/100,000",FXN,FXN,NBK1281,1996 +chrX,147912037,147912111,146993555,146993629,146176665,146176769,(GGC)35.0,FXS_FMR1,"FXS, FXTAS, POF1",+,CGG,CGG,CGG,,,,,"Fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency FXPOI/POF1",FMR1,,(CGG)*,XD,5' UTR,Exon 2,5–44,5,44,45-200,45,200,200-2000,200,2000,20.6667,3,"Typical: FXS 1 to ""first several yeares of life"", FXTAS 60-65 (GeneReview); Range: 0 (FXS, UptoDate) - 78 (PMID: 17427188)",0,78,1,65,ref,"LOF via decreased gene expression in FXS, GOF in FXTAS",Loss of function via transcriptional silencing in FXSRNA GOF in FXTAS,(doi.org/10.1038/nrg1691) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, NBK1384","FXTAS/POI 55–200, FXS >200, late onset",,74,300624; 300623,19/100000,"16-25/100,000 males; Tang et al., 2017: known carrier frequency 300-500/100,000 but detected was 11/100,000",FMR1,FMR1,NBK1384,1991 +chr14,92071012,92071053,92537356,92537397,86300520,86300603,(CTG)28.0,SCA3_ATXN3,"SCA3, MJD",-,CTG,CTG,AGC,,,,,Spinocerebellar Ataxia Type 3/Machado-Joseph Disease,ATXN3,,(CTG)*,AD,Coding,Second last exon,12–44,12,44,45-59,45,59,60-87,60,87,14.0,3,Typical: 10-49 (GeneReview); 5-73 (GeneReview; PMID: 30414314),5,73,10,49,ref,Polyglutamine ,Polyglutamine ,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x","""14:92071009-92071042""",,41,109150,2.1/100000,"1–5/100,000, Tang et al., 2017; Most prevalence SCA subtype (NBK557816)",ATXN3,ATXN3,NBK1196,1994 +chr3,129172577,129172659,128891420,128891502,131917483,131917557,(CAGG)18.8,DM2_CNBP,DM2,-,CAGG,CAGG,CCTG,,,,,Myotonic Dystrophy Type 2,CNBP,(CAGG)n(CAGA)10(CA)19,(CAGG)*(CAGA)*(CA)*,AD,Intronic,,11–26,11,26,27-74,27,74,"75-11,000",75,11000,20.8,4,Typical: 28-56 (PMID: 29086017); Range: 0-73 (PMID: 31159885),0,73,28,56,ref,Aberrant splicing,Aberrant splicing,(doi.org/10.1093/hmg/ddr568),"Hannan 2018, Mirkin 2007, GeneReviews NBK1466, https://doi.org/10.1038/s41580-021-00382-6",(TG)n(TCTG)n(CCTG)n. CCTG expansion causes DM2 but the other repeat units are also variable.,Penetrance is age-dependent and approaches 100%,82,602668,2.29/100000,"2.29/100,000 (PMID: 35483324); population specific prevalence (GeneReview)",CNBP,CNBP,NBK1466,2001 +chrX,148500605,148500753,147582125,147582273,146765191,146765342,(GCC)51.3,FRAXE_AFF2,FRAXE,+,GCC,GCC,CCG,,,,,"Fragile X syndrome, FRAXE type",AFF2,,(GCC)*,XR,5' UTR,5’ Region,4-39,4,39,,,,200-2000,200,2000,50.3,3,Typical: 2-10; Range: 1-10 (developmental delays without physical features can make onset difficult to detect until schooling),1,10,2,10,ref,"LOF, reduced gene expression",Loss of function via transcriptional silencing,(doi.org/10.1038/nrg1691) (doi.org/10.1007/s11604-022-01343-5),"Mirkin 2007, OMIM, GeneReviews NBK535148",,,148,309548,2/50000,"1-4/100,000 males (https://medlineplus.gov/genetics/condition/fragile-xe-syndrome); 1/50-100,000 males, more than 50 families (PMID: 11246464)",AFF2,AFF2,NBK535148,1993 +chr18,55586155,55586227,53253386,53253458,55789234,55789288,(AGC)18.3,FECD3_TCF4,FECD3,-,CAG,CAG,CTG,,,,,Fuchs endothelial corneal dystrophy 3,TCF4,,(CAG)*,AD,Intronic,Intron 1,10 - 40,10,40,,,,>50,50,150,25.3,3,Typical: 40-59 (PMID: 1676829); Range: 32 (PMID: 21245398) - 70 (PMID: 25168903),32,70,40,59,ref,RNA toxicity proposed,"""sequestration of MBNL1 in RNA foci, similar to the mechanism underlying myotonic dystrophy-1 """,(10.1074/jbc.M114.621607),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,"Penetrance is <100%; reduced penetrance has been reported in individuals with >80 CTG repeats [Wieben et al 2014]. Predominantly in women (~75%) (PMID: 16769829). “Although studies on the prevalence of FECD worldwide are limited, the disorder is thought to be more common in Eurasian populations, with its corneal manifestations documented in 11% of females and 7% of males in Reykjavik, Iceland,3 8.5 % of Singapore Chinese,4 and 5.5% of Japanese.4 (PMID: 25722209) ",72,613267,4.5/100,~4/100 (over 40) (OMIM); 5/100 (PMID: 20825314),TCF4,TCF4,NBK535148,2015 +chr12,6936717,6936775,7045880,7045938,6947904,6947941,(CAG)12.7,DRPLA_ATN1,DRPLA,+,CAG,CAG,AGC,,,,,Dentatorubral-Pallidoluysian Atrophy,ATN1,,(CAG)*,AD,Coding,Exon 5,3–35,3,35,,,,48-93,48,93,19.0,3,"Typical: 20-40 (PMID: 6808417, NBK1491) +Range: 0 (PMID: 11160976) - 72 (NBK1491)",0,72,20,40,ref,Polyglutamine,Polyglutamine,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",,,58,125370,4.5/1000000,"2-7/1,000,000",ATN1,ATN1,NBK1491,1994 +chrX,31284557,31284605,31302674,31302722,30882695,30882743,(TTC)22.7,DMD_DMD,DMD,-,TTC,TTC,AAG,,,,,Duchenne muscular dystrophy,DMD,,(TCC)*,XR,Intronic,,<33,16,33,,,,>59,59,82,16.7,3,Typical: 6-7 (usual disease is 0-3),6,7,6,7,ref,Protein LOF,Functional defect in dystrophin/dystroglycan,(https://doi.org/10.1007/s10038-006-0056-7),PMID: 27417533,,There is conflicting evidence for the association between this repeat expansion and Duchenne muscular dystrophy. The association was reported in a single family (PMID: 27417533). The population frequency of the proposed pathogenic allele is much higher than expected for a highly penetrant early-onset condition.,48,310200,4.8/100000,"Believed to be 0 for disease specific to STR expansion. 1/3500-4700 male births (incidence) for overall DMD (one of the most common and severe congenital myopathies). 4.8/100,000 prevalence PMID: 35168641",DMD,DMD,NBK535148, +chr19,45770204,45770266,46273462,46273524,48597739,48597756,,DM1_DMPK,DM1,-,CAG,CAG,CTG,,,,,Myotonic Dystrophy Type 1,DMPK,,(CAG)*,AD,3' UTR,Last exon,5–34,5,34,35-49,35,49,50-1000,50,1000,20.7,3,"Typical: 10-30 (""classic"", GeneReview); Range: 0-74 (PMID: 38454488)",0,74,10,30,ref,RNA GOF,RNA gain-of-function - RNA gelation leading to misregulation of alternative splicing,(doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK1165, s40478-021-01201-x",Interruptions: CCG,,62,160900,8/100000,"5-20/100,000 (GeneReview); Tang et al., 2017: 0.5-18.1/100,000; 6.5/100,000 (PMID: 31159885) ; 9.27 cases (95% CI: 4.73-15.21) per 100,000, ranging from 0.37 to 36.29 cases per 100,000 (PMID: 35483324)",DMPK,DMPK,NBK1165,1992 +chr2,100104799,100104824,100721261,100721286,100563686,100563738,(GCC)17.7,FRA2A_AFF3,FRA2A,-,GCC,GCC,CGG,,,,,Intellectual disability associated with fragile site FRA2A,AFF3,,(GCC)*,AD,Intronic,Intron ,3-20,3,20,,,,300,300,300,8.7,3,Early childhood (small sample size) (PMID: 24763282),1,7,,,ref,"Decreased gene expression, methylation","""silencing of the FMR2 gene as a consequence of a CCG expansion located upstream of this gene""",malacard,"https://doi.org/10.1038/s41580-021-00382-6, PMC3998887","Path threshold may actually be higher than 300, assay was not sensitive enough",,25,601464,,"1/862 (1/654-1266) population prevalence of methylated AFF3 expansions (mild cognitive disability) https://www.medrxiv.org/content/10.1101/2023.05.03.23289461v1.full.pdf ",,,,2014 -chrX,67545317,67545419,66765159,66765261,65975148,65975250,(GCA)33.3,SBMA_AR,SBMA,+,GCA,GCA,AGC,,,,,"Spinal and bulbar muscular atrophy, Kennedy Disease",AR,,(GCA)*,XR,Coding,Exon 1,9–34,9,34,36-37,36,37,38–68,38,68,34.0,3,"Typical: 20-49 (OMIM), Range: 15-75 (https://doi.org/10.1038/sj.ejhg.5200656) ",20,49,15,75,ref,Polyglutamine,Polyglutamine,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",,Possibly only in men (OMIM). Weak correlation between repeat length and age of onset; possibly specific to Japanese population. (PMID: 11436124),102,313200,"1/30,000","1-2/100,000 (population-specific, higher in Finnish population, Canadian population) (PMID: 37628685); 1/30,000 (Orphanet) ; mutation frequency of 1:3182 10x more frequent than reported disease prevalence of 1 in 30,000 (PMID: 36797998); Tang et al., 2017: 0.67-2.5/100,000",AR,AR,NBK1333,1991 -chrX,25013649,25013697,25031766,25031814,24597886,24597934,(GCC)14.7,EIEE1_ARX,EIEE1,-,NGC,NGC,CNG,,,,,Early-infantile epileptic encephalopathy,ARX,,(NGC)*,XR,Coding,Exon 2,10-16,10,16,,,,17-27,17,27,14.7,3,"Typical: 0 (PMID: 21204215, PMID: 9307258, OMIM) -Range: 0-4 (Childhood epilepsy, cognitive disability, ∼70% of cases infantile spasms --> seizures by 3 or 4 years re: PMID: 19587282)",0,0,0,4,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"GeneReviews NBK535148, OMIM",Exon 2 aa 110-115,,43,308350; 300419; 300215,N/A,Unknown,ARX_1,ARX_1,NBK535148, -chrX,25013530,25013565,25031647,25031682,24597767,24597799,(GGCCGCGGCGGCCGC)2.2,PRTS_ARX,PRTS,-,NGC,NGC,CNG,,,,,Partington syndrome,ARX,,(NGC)*,XR,Coding,Exon 2,12,12,12,,,,20,20,20,12.0,3,"Typical: 1-3; Range: 0-4 (OMIM); Mildness can make diagnosis difficult (particularly mild/absent in females) ",0,4,1,3,ref,Polyalanine,Polyalanine,(OMIM) (doi.org/10.1007/s11604-022-01343-5),"GeneReviews NBK535148, OMIM","Novel, Exon 2 aa 144-155",,35,309510,N/A,Unknown,ARX_2,ARX_2,NBK535148, -chr12,6936717,6936775,7045880,7045938,6947904,6947941,(CAG)12.7,DRPLA_ATN1,DRPLA,+,CAG,CAG,AGC,,,,,Dentatorubral-Pallidoluysian Atrophy,ATN1,,(CAG)*,AD,Coding,Exon 5,3–35,3,35,,,,48-93,48,93,19.0,3,"Typical: 20-40 (PMID: 6808417, NBK1491) -Range: 0 (PMID: 11160976) - 72 (NBK1491)",20,40,0,72,ref,Polyglutamine,Polyglutamine,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",,Size correlates with disease severity; infantile cases are extremely large. Juvenile-onset (also referred to as childhood- or early-onset) DRPLA is generally associated with ≥65 CAG repeats. Adult-onset (late-onset) associated with <65 CAG repeats. Thought to be almost fully penetrant. (GeneReview),58,125370,"4.5/1,000,000","2-7/1,000,000",ATN1,ATN1,NBK1491,1994 -chr6,16327634,16327724,16327865,16327955,16200189,16200282,(TGC)31.1,SCA1_ATXN1,SCA1,-,CTG,CTG,AGC,,,,,Spinocerebellar Ataxia Type 1,ATXN1,,(CTG)*,AD,Coding,Exon 8,6–35,6,35,36-38,36,38,39–91,39,91,30.3,3,Typical: 20-39 (UptoDate); Range: 6(PMID: 3165612)-63 (PMID: 8825276),6,63,20,39,ref,Polyglutamine,Polyglutamine,(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK1184, s40478-021-01201-x",Interruptions: CAT,Penetrance >95%; age-dependent (GeneReview),90,164400,"1.5/100,000","1-2/100,000",ATXN1,ATXN1,NBK1184,1993 -chr22,45795355,45795424,46191235,46191304,46280060,46280129,(ATTCT)15.0,SCA10_ATXN10,SCA10,+,ATTCT,ATTCT,ATTCT,,,,,Spinocerebellar Ataxia Type 10,ATXN10,,(ATTCT)*,AD,Intronic,Intron 9/11,10–32,10,32,280-850,280,850,800-4500,800,4500,14.0,5,Typical: 12-48; Range: 11-83 (NBK1175),11,83,12,48,ref,Unknown,Transdominant mechanism theorized,(malacard),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",Interruptions: ATCCT,Age of onset influenced by allele size (determines ~1/3) alongside other factors (GeneReview),69,603516,N/A,Unknown; >300 individuals (GeneReview),ATXN10,ATXN10,NBK1175,2000 -chr12,111598950,111599019,112036754,112036823,111575873,111575940,(GCT)22.3,SCA2_ATXN2,SCA2,-,CTG,CTG,AGC,,,,,Spinocerebellar Ataxia Type 2,ATXN2,,(CTG)*,AD/AR,Coding,Exon 1,14–31,14,31,32-34,32,34,33–200,33,200,23.3,3,Typical: 30-39 (GeneReview); Range: 2-86 (OMIM),2,86,30,39,ref,"Polyglutamine ","Polyglutamine ",(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, GeneReviews NBK1275, s40478-021-01201-x","29–32 repeats: increased ALS risk, Interruptions: CAA, CGG, CGC. Parkinson disease, late-onset, susceptibility.",Wide range of onset with inverse correlationm between allele size and age of onset.,69,183090,"1.5/100,000","1-2/100,000 (Tang et al., 2017) (population dependent)",ATXN2,ATXN2,NBK1275,1996 -chr14,92071012,92071053,92537356,92537397,86300520,86300603,(CTG)28.0,SCA3_ATXN3,"SCA3, MJD",-,CTG,CTG,AGC,,,,,Spinocerebellar Ataxia Type 3/Machado-Joseph Disease,ATXN3,,(CTG)*,AD,Coding,Second last exon,12–44,12,44,45-59,45,59,60-87,60,87,14.0,3,Typical: 10-49 (GeneReview); 5-73 (GeneReview; PMID: 30414314),5,73,10,49,ref,"Polyglutamine ","Polyglutamine ",(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x","""14:92071009-92071042""","Three subsets with different ranges in ages of onset; penetrance is age related and approaches 100%, with allele size impacting disease velocity and age of onset (PMID: 32978817)",41,109150,"2.1/100,000","1–5/100,000, Tang et al., 2017; Most prevalence SCA subtype (NBK557816)",ATXN3,ATXN3,NBK1196,1994 -chr3,63912685,63912716,63898361,63898392,63956303,63956334,(GCA)10.7,SCA7_ATXN7,SCA7,+,CAG,CAG,AGC,,,,,Spinocerebellar Ataxia Type 7,ATXN7,(CAG)n(CCG)4,(CAG)*(CCG)+,AD,Coding,"Exon 1, 2, or 3 (depending on isoform)",4–19,4,19,28-35,28,35,34–460,34,460,10.7,3,Typical: 4-48 (PMID: 20739808); Range: 0-65 (GeneReview),0,65,4,48,ref,"Polyglutamine ","Polyglutamine ",(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",,"Extremely variability in age of onset, inversely related to allele size (GeneReview)",31,164500,".999/300,000","<1/300,000 (GeneReview)",ATXN7,ATXN7,NBK1256,1996 -chr13,70139383,70139429,70713515,70713561,69361244,69361271,(CTG)9.3,SCA8_ATXN8OS,SCA8,+,CTG,CTG,CTG,,,,,Spinocerebellar Ataxia Type 8,ATXN8OS,(CTA)10(CTG)n,(CTA)*(CTG)*,AD,3' UTR,Exon 5 or 3’ UTR depending on transcript,15–50,15,50,50-70,50,70,71-1300,71,1300,15.3,3,Typical: 20-40; Range: 0-73 (GeneReview),1,73,20,49,ref,"Polyglutamine/toxic gain-of-function; Unknown ","Polyglutamine/toxic gain-of-function; Unknown ",(OMIM) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x","Two genes span the CTG/CAG repeat and are expressed in opposite directions: ATXN8, which encodes a nearly pure polyglutamine expansion protein in the CAG direction, and ATXN8OS (603680), which, when transcribed, produces a noncoding CUG expansion RNA (Moseley et al., 2006). Roda et al. suggested that the ATXN8 or ATXN8OS gene should not be evaluated in isolation as a candidate gene for spinocerebellar degenerative disease",,46,608768,"0.5/100,000","<1/100,000; Tang et al., 2017; Expansion in 1:100-1200 chromosomes (GeneReview)",ATXN8OS,ATXN8OS,NBK1268,1999 -chr16,66490397,66490466,66524300,66524369,72284667,72284761,(AATAA)19.4,SCA31_BEAN1,SCA31,+,AATAA,"TGGAA,TAGAA","AATGG,AATAG",,,"AAAAA,AAAAC,AAATG,AGAAA,ATAAG,TAAAC,TAACA,TACAA,TCAAA,TGCAA","AAAAA,AAAAC,AAATG,AAAAG,AAGAT,AAACT,AACAT,AATAC,AAATC,AATGC",Spinocerebellar Ataxia Type 31,BEAN1,,(TGGAA)*(TAGAA)*,AD,Intronic,Intron 4/4,0-10,0,10,,,,>110,110,760,14.4,5,"Typical: 56-62 (PMID: 36563608); Range: 8-83 (PMID: 23331413) ",8,83,56,62,novel,Epigenetic,"Role in heterochromatin or chromosomal structure theorized ",(OMIM),"OMIM, Sato 2009, 19878914 (Pubmed), https://doi.org/10.1038/s41580-021-00382-6","Novel, STR-containing insertion, not present in reference genome: Reds disagree on normal/pathogenic sizes",,69,117210,N/A,Unknown (more common in Japanese pop),BEAN1,BEAN1,NBK535148,2009 -chr9,27573484,27573546,27573482,27573544,27584063,27584155,(GCCCCG)15.8,FTDALS1_C9orf72,FTDALS1,-,GGCCCC,GGCCCC,CCGGGG,,,,,Frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS),C9orf72,,(GGCCCC)*,AD,Intronic,Intron 1 or 5' depending on transcript,3–25 (2-19 Reds),2,20,20-60,20,60,250-2000,250,2000,10.8,6,Typical: 50-64; Range: 20-91 (GeneReview),20,91,50,64,ref,RNA toxicity proposed,"""The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA/DNA hybrids (R-loops). The structural polymorphism causes a repeat length-dependent accumulation of transcripts aborted in the HRE region.""",OMIM,"Hannan 2018, GeneReviews NBK535148, OMIM, s40478-021-01201-x",,,62,105500,N/A,"The expansion of a hexanucleotide repeat GGGGCC in C9orf72 is the most common known cause of ALS accounting for ~ 40% familial cases and ~ 7% sporadic cases in the European population; overall ALS incidence is 1-2/100,000 person-years, point prevalence is 3-5/100,000 (Europe/US); lifetime risk is 1 in 300 (PMID: 31315673). C9orf72-FTD is estimated to be 0.04-134:100,000 (GeneReview), and by our estimates 0.65-1.56/100,000 for C9orf72-ALS. ",C9ORF72,C9ORF72,NBK268647,2011 -chr19,13207859,13207898,13318673,13318712,13333137,13333176,(CTG)13.3,SCA6_CACNA1A,SCA6,-,CTG,CTG,AGC,,,,,Spinocerebellar Ataxia Type 6,CACNA1A,,(CTG)*,AD,Coding,Last Exon: 47 or 48,4–18,4,18,19,19,19,20–33,20,33,13.3,3,Typical: 43-52 (GeneReview); Range: 16 (PMID: 23331413) - 73 (NBK1140),16,73,43,52,ref,"Polyglutamine ","Polyglutamine ",(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",,,39,183086,"0.3/100,000","13-15% of global SCA prevalence, estimated to be 0.02-31/100,000 (GeneReview); Tang et al., 2017: 0.3-5/100,000",CACNA1A,CACNA1A,NBK1140,1997 -chr11,119206289,119206322,119076999,119077032,119226663,119226696,(CGG)11.3,JBS_CBL,JBS,+,CGG,CGG,CGG,,,,,Jacobsen syndrome (FRAX11B fragile site),CBL,,(CGG)*,AD,5' UTR,,<79,11,79,,,,>100,100,100,11.3,3,Condition at birth.,0,0,0,0,ref,,No information found,(OMIM),"https://doi.org/10.1038/s41580-021-00382-6, 7603564 (PubMed)",,,33,147791,"1/100,000","1/100,000 births; female/male ratio 2:1 (PMID: 19267933)",CBL,,, -chr19,18786034,18786049,18896844,18896859,18921630,18921645,,EDM1-PSACH_COMP,"EDM1, PSACH",-,GTC,GTC,ACG,,,,,"Multiple epiphyseal dysplasia, Pseudoachondroplasia",COMP,,(GTC)*,AD,Coding,,5,5,5,,,,4 or 6-7,6,7,5.0,3,Typical: 0-2 (COMP-PSACH)/ 1-12 (EDM1); Range: 0 (PSACH) - 13 (EDM1),0,13,0,12,ref,Protein LOF,"LOF, domain dependent",(https://pubmed.ncbi.nlm.nih.gov/29530484/),Pathogenic Short Tandem Repeats Gnomad v3.1.2,"Two diseases, same locus. Both expansions and contractions associated with disease","Disease phenotypic spectrum based on repeat length, with penetrance 100%. Contraction may also be potentially pathogenic (2-4 repeats from normal 5).",15,132400; 177170,N/A,"Specific contribution of COMP repeats to EDM1 is unknown (~300 COMP mutation variants for both phenotypes); likely 1:90,000 prevalence for COMP-PSACH that is repeat-specific.",COMP,COMP,NBK1123; NBK1487, -chr1,57367044,57367125,57832716,57832797,57245936,57245977,(AAAAT)8.6,SCA37_DAB1,SCA37,-,AAAAT,GAAAT,ATTTC,,,AAAAA,TTTTT,Spinocerebellar Ataxia Type 37,DAB1,,(AAAAT)*(GAAAT)*(AAAAT)*,AD,Intronic,Intron 1 (most isoforms),0-16,0,16,,,,31-75,31,75,16.6,5,Typical: 33-53; Range: 18-64 (GeneReview),33,53,18,64,novel,Protein toxic GOF,toxic gain-of-function mechanism,(OMIM),"Seixas et al 2017 AJHG, NBK541729, s40478-021-01201-x","Novel. Normal: [(ATTTT)7–400] Pathogenic: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90], ATTTC within (ATTTT)7–400 repeat region",Lifelong penetrance at 100% with variable age of onset.,81,615945,N/A,"0.20/100,000 specific to Portugal; not yet found in other geographic regions",DAB1,DAB1,NBK541729,2017 -chr12,50505002,50505022,50898785,50898805,50468096,50468116,,FRA12A_DIP2B,FRA12A,+,GGC,GGC,CGG,,,,,"Intellectual developmental disorder, FRA12A type",DIP2B,,(GGC)*,AD,5' UTR,,6-23,6,23,~139-206,139,206,~273-306,273,306,7.0,3,Typical: 0-1 (PMID: 3742859); Range: 0-3 (PMID: 4042396),0,3,0,1,ref,"Increased gene expression, methylation","Increased gene expression, methylation","(OMIM, https://www.medrxiv.org/content/10.1101/2022.09.12.22279739v3.full-text)","OMIM, NBK535148, https://www.medrxiv.org/content/10.1101/2022.09.12.22279739v3.full-text",,No consistent phenotype and variable penetrance. Repeat elongation increases expression.,20,136630,N/A,N/A,DIP2B,DIP2B,NBK535148, -chrX,31284557,31284605,31302674,31302722,30882695,30882743,(TTC)22.7,DMD_DMD,DMD,-,TTC,TTC,AAG,,,,,Duchenne muscular dystrophy,DMD,,(TCC)*,XR,Intronic,,<33,16,33,,,,>59,59,82,16.7,3,Typical: 6-7 (usual disease is 0-3),6,7,6,7,ref,Protein LOF,Functional defect in dystrophin/dystroglycan,(https://doi.org/10.1007/s10038-006-0056-7),PMID: 27417533,,There is conflicting evidence for the association between this repeat expansion and Duchenne muscular dystrophy. The association was reported in a single family (PMID: 27417533). The population frequency of the proposed pathogenic allele is much higher than expected for a highly penetrant early-onset condition.,48,310200,1/4100,Believed to be 0 for disease specific to STR expansion. 1/3500-4700 for overall DMD (one of the most common and severe congenital myopathies).,DMD,DMD,NBK535148, -chr19,45770204,45770266,46273462,46273524,48597739,48597756,,DM1_DMPK,DM1,-,CAG,CAG,CTG,,,,,Myotonic Dystrophy Type 1,DMPK,,(CAG)*,AD,3' UTR,Last exon,5–34,5,34,35-49,35,49,50-1000,50,1000,20.7,3,"Typical: 10-30 (""classic"", GeneReview); Range: 0-74 (PMID: 38454488)",0,74,10,30,ref,RNA GOF,RNA gain-of-function - RNA gelation leading to misregulation of alternative splicing,(doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK1165, s40478-021-01201-x",Interruptions: CCG,Almost 100% penetrance by 50 years; correlation with age of onset and allele size until plateau around 1.2 kB (OMIM),62,160900,"6.5/100,000","5-20/100,000 (GeneReview); Tang et al., 2017: 0.5-18.1/100,000; 6.5/100,000 (PMID: 31159885)",DMPK,DMPK,NBK1165,1992 -chrX,147912037,147912111,146993555,146993629,146176665,146176769,(GGC)35.0,FXS_FMR1,"FXS, FXTAS, POF1",+,CGG,CGG,CGG,,,,,"Fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency FXPOI/POF1",FMR1,,(CGG)*,XD,5' UTR,Exon 2,5–44,5,44,45-200,45,200,200-2000,200,2000,20.6667,3,"Typical: FXS 1 to ""first several yeares of life"", FXTAS 60-65 (GeneReview); Range: 0 (FXS, UptoDate) - 78 (PMID: 17427188)",0,78,1,65,ref,"LOF via decreased gene expression in FXS, GOF in FXTAS",Loss of function via transcriptional silencing in FXSRNA GOF in FXTAS,(doi.org/10.1038/nrg1691) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, NBK1384","FXTAS/POI 55–200, FXS >200, late onset",,74,300624; 300623,"19/100,000","16-25/100,000 males; Tang et al., 2017: known carrier frequency 300-500/100,000 but detected was 11/100,000",FMR1,FMR1,NBK1384,1991 -chr3,138946020,138946062,138664862,138664904,141687014,141687051,(GCGGCTGCAGCCGCA)2.5,BPES_FOXL2,BPES,-,NGC,NGC,CNG,,,,,"Blepharophimosis, epicanthus inversus, and ptosis",FOXL2,,(NGC)*,AD,Coding,Exon 1,<14,14,14,,,,>15,15,15,14.0,3,0 (birth),0,0,0,0,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),NBK535148,,,42,110100,"0.31/50,000","1 in 50,000 births globally for all BPES, with FOXL2 expansions 31% of pathogenic variants (NBK1441; NBK535148)",FOXL2,FOXL2,NBK1441,2001 -chr9,69037286,69037304,71652202,71652220,81210843,81210861,(AAG)9.7,FRDA_FXN,FRDA,+,GAA,GAA,AAG,,,,,Friedreich ataxia,FXN,(A)16(GAA)n,(A)*(GAA)*,AR,Intronic,Intron 1,5–33,5,33,34-65,34,65,66 to 1700,66,1700,6.0,3,Typical: 10-15; Range: 2-80 (GeneReview),2,80,10,15,ref,"LOF, reduced gene expression",Loss of function via transcriptional silencing,(doi.org/10.1038/nrg1691) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148",Not annotated by TRF?,,2,229300,"1/50,000","1/50,000 (OMIM); Tang et al., 2017: Known carrier frequency 1000/100,000; observed 421/100,000",FXN,FXN,NBK1281,1996 -chr19,14496041,14496074,14606853,14606886,14622656,14622702,(CCG)15.7,OPDM2_GIPC1,OPDM2,-,CCG,CCG,CGG,,,,,Oculopharyngodistal myopathy,GIPC1,,(CCG)*,AD,5' UTR,Exon 1,6-29,6,29,,,,70-138,70,138,14.7,3,Typical: 20-34 (PMID: 32413282); Range: 14 (PMID: ...282) - 70 (PMID: 33374016),14,70,20,34,ref,RNA toxicity,RNA mediated toxicity hypothesized; unknown,"(OMIM), (doi.org/10.1007/s11604-022-01343-5)","Pathogenic Short Tandem Repeats Gnomad v3.1.2, 32413282 (Pubmed)",,,33,618940,N/A,Population dependent; presumed rare.,GIPC1,GIPC1,NBK535148,2020 -chr2,190880873,190880920,191745599,191745646,191369983,191370024,(GCA)14.0,GDPAG_GLS,GDPAG,+,GCA,GCA,AGC,,,,,Glutaminase deficiency,GLS,,(GCA)*,AR,5' UTR,Exon 1,5-26,5,26,,,,90 - 1500,90,1500,16.0,3,"Early childhood (2-4; PMID: 30970188, 35913761)",2,4,2,4,ref,"Decreased gene expression, methylation",Change in histone modification decreases transcription,(OMIM),"van Kuilenburg 2019 NEJM, 30970188 (Pubmed)",Several compound het cases reported,,47,618412,N/A,"As of 2019, only 7 cases total of GLS deficiency, including non-repeat",GLS,GLS,NBK535148,2019 -chr7,27199678,27199732,27239297,27239351,27335815,27335849,(GCCGCGGCCGCCGCCG)1.9,HFG_HOXA13-III,HFG-III,-,NGC,NGC,CNG,,,,,Hand-foot-genital syndrome 3,HOXA13,,(NGC)*,AD,Coding,Exon 1,8-18,8,18,,,,24-32,24,32,18.0,3,0 (birth),0,0,0,0,ref,"Polyalanine ","Polyalanine ",(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK1423",There are 3 pathogenic polyalanine tracts in this gene,,54,140000,N/A,"""Extremely rare"" (GeneReview)",HOXA13_3,HOXA13_3,NBK1423,2000 -chr7,27199825,27199861,27239444,27239480,27335914,27335954,(GCAGCCGCCGCCGCT)2.9,HFG_HOXA13-II,HFG-II,-,NGC,NGC,CNG,,,,,Hand-foot-genital syndrome 2,HOXA13,,(NGC)*,AD,Coding,Exon 1,12,12,12,,,,18,18,18,12.0,3,0 (birth),0,0,0,0,ref,"Polyalanine ","Polyalanine ",(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK1423",There are 3 pathogenic polyalanine tracts in this gene,,36,140000,N/A,"""Extremely rare"" (GeneReview)",HOXA13_2,HOXA13_2,NBK1423,2000 -chr7,27199924,27199966,27239543,27239585,27335920,27335951,(GCAGCCGCCGCCGCT)2.7,HFG_HOXA13-I,HFG-I,-,NGC,NGC,CNG,,,,,Hand-foot-genital syndrome 1,HOXA13,,(NGC)*,AD,Coding,Exon 1,14,14,14,,,,22,22,22,14.0,3,0 (birth),0,0,0,0,ref,"Polyalanine ","Polyalanine ",(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats, Gnomad v3.1.2, NBK1423",There are 3 pathogenic polyalanine tracts in this gene,,42,140000,N/A,"""Extremely rare"" (GeneReview)",HOXA13_1,HOXA13_1,NBK1423,2000 -chr2,176093058,176093103,176957786,176957831,176581179,176581220,(GGC)14.0,SD5_HOXD13,SD5,+,GCN,GCN,CNG,,,,,Syndactyly,HOXD13,,(GCN)*,AD,Coding,Exon 1,< 15,14,15,,,,>22,22,22,14.0,3,0 (birth),0,0,0,0,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,45,186000,N/A,3 individuals (GeneReview),HOXD13,HOXD13,NBK535148,1996 -chr4,3074877,3074940,3076604,3076667,3073604,3073694,(CAG)30.3,HD_HTT,HD,+,CAG,CAG,AGC,,,,,Huntington disease,HTT,(CAG)nCAACAG(CCG)12,(CAG)*CAACAG(CCG)*,AD,Coding,Exon 1,6–26,6,26,"27-35 unstable, 36-39 reduced penetrance",27,39,40–250 (>60 assocated with onset age <20),40,250,21.3,3,Typical: 35-44 (GeneReview); Range: 2-85 (PMID: 21171977),2,85,35,44,ref,"Polyglutamine ","Polyglutamine ",(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews, PMID: 12791042",CAG exp only pathogenic. Interruptions impact pathogenicity.,,63,143100,,"1/10,000",HTT,HTT,NBK1305,1993 -chr16,87604283,87604329,87637889,87637935,93675724,93675776,(GCT)17.3,HDL2_JPH3,HDL2,+,CTG,CTG,CTG,,,,,Huntington disease-like 2,JPH3,,(CTG)*,AD,Coding,Exon 2,6–28,6,28,29-39,29,39,40–58,40,58,15.6667,3,Typical: 30-52; Range: 12-66 (GeneReview),12,66,30,52,ref,,"""unstable vertical transmission""",(doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK1529",reflen + pos from HipSTR,,46,606438,,"<1/1,000,000",JPH3,JPH3,NBK1529,2001 -chr8,104588972,104588999,105601200,105601227,105716410,105716441,(CGC)10.7,OPDM1_LRP12,OPDM1,-,CGC,CGC,CGG,,,,,Oculopharyngodistal myopathy type 1,LRP12,,(CGC)*,AD,5' UTR,,13-45,13,45,,,,90,90,90,11.7,3,Typical: 31-51 (PMID: 34047774); Range: 7-66 (PMID: 2124290),7,66,31,51,ref,RNA toxicity,RNA mediated toxicity hypothesized; unknown,"(OMIM), (doi.org/10.1007/s11604-022-01343-5)","OMIM 164310, Ishiura et al [2019], Ehdn, NBK535148, PMID 31332380",CGG/CGT,,27,164310,N/A,Population dependent; unknown percentage of LRP12 pathogenic variants.,LRP12,LRP12,NBK1126,2019 -chr5,10356339,10356411,10356451,10356523,10295521,10295593,(TTTTA)14.8,FAME3_MARCHF6,FAME3,+,TTTTA,TTTCA,ATTTC,,,"ATGTT,TAGTT,TTTTG,TTTTT","ATGTT,AGTTT,GTTTT,TTTTT",Familial adult myoclonic epilepsy type 3,MARCHF6,,(TTTTA)*(TTTCA)*,AD,Intronic,Intron 1,0,,,,,,"791-1,035 repeats",791,1035,14.8,5,Typical: 24-41 (PMID: 19616813); Range: 10 (OMIM) - 46 (PMID: 31664039),10,46,24,41,novel,Unknown,Noted as unknown in literature,(OMIM),"Florian, R.T. Nat Comm. 2019",TTTTA + TTTCA,,72,613608,N/A,"Overall FAME prevalence is < 1/35,000; MARCHF6-caused much smaller",MARCHF6,MARCHF6,NBK535148,2019 -chr15,22786677,22786701,23086366,23086390,20458505,20458536,(GCG)10.7,ALS1_NIPA1,ALS1,+,GCG,GCG,CGG,,,,,Amyotrophic lateral sclerosis,NIPA1,,(GCG)*,AD,Coding,,6-10,6,10,,,,> 11,11,56,10.7,3,Typical: 44-60 (PMID: 26777436); Range: 25 (PMID: 22378146) - 77 (PMID: ...346),25,77,44,60,ref,,No information found,N/A in GeneCard,"Pathogenic Short Tandem Repeats Gnomad v3.1.2, 30342764 (Pubmed), path range from gnomAD",Proposed modifier for ALS,,24,105400,,"2.7-7.4/100,000 (All ALS, not just this locus)",NIPA1,NIPA1,, -chr20,2652733,2652757,2633379,2633403,2683200,2683224,(GCCTGG)8.8,SCA36_NOP56,SCA36,+,GGCCTG,GGCCTG,CCTGGG,,,,,Spinocerebellar ataxia type 36,NOP56,(GGCCTG)n(CGCCTG)3,(GGCCTG)*(CGCCTG)*,AD,Intronic,Intron 1,3 to 14,3,14,15-649,15,649,650-2500,650,2500,7.2,6,Typical: 40-60 (GeneReview); Range: 28 (PMID: 37810464) - 67 (PMID: 37332636),28,67,40,60,ref,Protein toxic GOF,toxic gain-of-function mechanism,(OMIM),"GeneReviews, OMIM, NBK231880",,,42,614153,,Unknown,NOP56,NOP56,,2011 -chr1,149390803,149390842,145209324,145209354,148519696,148519738,(GGC)14.3,NIID_NOTCH2NLC,NIID,+,GGC,GGC,CGG,,,,,"Neuronal intranuclear inclusion disease, Alzheimer disease and parkinsonism phenotype",NOTCH2NLC,,(GGC)*,AD,5' UTR,5' Region,7–39,7,39,,,,66-517,66,517,13.3,3,Typical: 30-70 (OMIM); Range: 10 (PMID: 37090934) - 78 (PMID: 37305750),10,78,30,70,ref,Unknown,May relate to methylation or RNA pathogenicity; Unknown,(OMIM) (doi.org/10.1007/s11604-022-01343-5),"doi: 10.1038/s41588-019-0458-z, https://doi.org/10.1016/j.ajhg.2019.05.013, s40478-021-01201-x","May be issues with parology between genes: C253572.1, NOTCH2, NOTCH2NL, NBPF14, NBPF19 ?? Motif variation in controls: (AGG)(CGG)n(AGG)0-3(CGG)0-2. Methylation involved",,39,603472,,Unknown,NOTCH2NLC,NOTCH2NLC,NBK535148,2019 -chr10,79826383,79826404,81586139,81586160,80695712,80695748,(GCG)12.7,OPML1_NUTM2B-AS1,OPML1,+,GGC,GGC,CGG,,,,,Oculopharyngeal myopathy with leukoencephalopathy 1,NUTM2B-AS1,,(GGC)*,AD,lncRNA,Exon 1 (noncoding),3-16,3,16,,,,>700,700,700,7.0,3,15-40 (PMID: 31332380; only characterized in one family),15,40,15,40,ref,RNA toxicity,"RNA mediated toxicity hypothesized, unknown",(OMIM) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, Ishiura 2019, doi: 10.1038/s41588-019-0458-z, https://doi.org/10.1038/s41580-021-00382-6","Not in TRF annotation, alt transcript in opposite direction: LOC642361",,21,618637,N/A,"""Rare""",NUTM2B-AS1,NUTM2B-AS1,NBK535148,2019 -chr14,23321472,23321502,23790681,23790711,17522488,17522518,,OPMD_PABPN1,OPMD,+,GCN,GCN,CNG,,,,,Oculopharyngeal muscular dystrophy,PABPN1,,(GCN)*,AD/AR,Coding,Exon 1,10,10,10,,,,12-17,12,17,7.0,3,Typical: 40-59 (PMID: 37519616); Range: 20-79 (PMID: 35112761),20,79,40,59,ref,"Polyalanine ","Polyalanine ",(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Mirkin 2007, GeneReviews NBK1126, s40478-021-01201-x","AR for 11 repeats, AD >12 repeats. Most known patients have (GCG)+, but GCN or any polyalanine may be pathogenic",,20,164300,,"1/100,000 Western countries",PABPN1,PABPN1,NBK1126,1998 -chr4,41745972,41746032,41747989,41748049,41719745,41719805,(GCC)15.7,CCHS_PHOX2B,CCHS,-,GCN,GCN,CNG,,,,,Congenital central hypoventilation syndrome,PHOX2B,,(GCN)*,AD,Coding,Exon 3,20,15,20,24,24,24,25-33,25,33,15.7,3,Typical: 0-2 (GeneReview/PMID: 15121777); Range: 0-36 (PMID: 16873766),0,36,0,2,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Mirkin 2007, GeneReviews NBK1427, s40478-021-01201-x",ReferenceRegion: 4:41745971-41746032,,46,209880,,1:148000-200000 births (Estimated),PHOX2B,PHOX2B,NBK1427,2003 -chr15,89333589,89333629,89876820,89876860,87088412,87088452,(GCT)13.7,CPEO_POLG,CPEO,-,GCT,GCT,AGC,,,,,"Progressive external ophthalmoplegia, Parkinson’s disease",POLG,,(CTG)*TTG(CTG)*,,,,10,10,10,,,,Deviation from 10 may impart disease risk with variable penetrance,,,13.7,3,Typical: 57 (PMID: 20399836) - 59 (PMID: 20826197); Range: 23-87 (PMID: ...836),23,87,57,59,ref,,No information found,N/A in GeneCard,"PMC2905783, PMID: 20399836, PMID: 10196696",Unconfirmed association,There is conflicting evidence for the association between this repeat expansion and Parkinson's risk (PMID: 20399836 and PMID: 10196696). Deviation from 10 may impart disease risk with variable penetrance.,40,Disease association unclear,,,,,, -chr5,146878728,146878759,146258291,146258322,147414734,147414765,(GCT)15.7,SCA12_PPP2R2B,SCA12,-,GCT,GCT,AGC,,,,,Spinocerebellar ataxia type 12,PPP2R2B,,(GCT)*,AD,Promoter,,4–32,4,32,,,,51–78,51,78,10.7,3,Typical: 26-50; Range: 8-56 (OMIM),8,56,26,50,ref,Unknown,Noted as unknown in literature,"N/A in GeneCard,","Hannan 2018, Mirkin 2007, OMIM, NBK535148, s40478-021-01201-x",(Roda et al. suggested that the ATXN8 or ATXN8OS gene should not be evaluated in isolation as a candidate gene for spinocerebellar degenerative disease),,31,604326,,Unknown,PPP2R2B,PPP2R2B,NBK535148,1999 -chr9,130681606,130681639,133556993,133557026,142886569,142886595,(CGC)9.0,HSAN-VIII_PRDM12,HSAN VIII,+,GCC,GCC,CCG,,,,,Hereditary sensory and autonomic neuropathy type VIII,PRDM12,,(GCC)*,AR,Coding,Exon,<14,12,14,,,,>18,18,19,12.0,3,0 (birth),0,0,0,0,ref,"LOF, epigenetic","""mutations abrogated the histone-modifying potential of PRDM12, consistent with a loss of function""",OMIM,"Pathogenic Short Tandem Repeats Gnomad v3.1.2, https://doi.org/10.1038/ng.3308",,,33,616488,,"<1/1,000,000",PRDM12,PRDM12,NBK535148, -chr4,159342527,159342618,160263679,160263770,162693304,162693405,(TTTTA)20.4,FAME7_RAPGEF2,FAME7,+,TTTTA,TTTCA,ATTTC,,,"TTTTT,TTATG","TTTTT,ATGTT",Familial adult myoclonic epilepsy type 7,RAPGEF2,,(TTTTA)*(TTTCA)*(TTTTA)*,AD,Intronic,Intron 14,0-1,0,1,,,,>=60,60,60,17.4,5,Typical: 20-33 (PMID: 30351492); Range: 18 (PMID: 29507423) - 37 (PMID: ...492),18,37,20,33,novel,RNA toxicity,RNA toxicity hypothesized,(10.1038/s41588-018-0067-2),"Ishiura 2018, 29507423 (Pubmed), https://sci-hub.hkvisa.net/10.1111/ene.13848","Novel, (TTTTA)exp(TTTCA)exp(TTTTA)n, but only the TTTCA is specific to affected individuals, Alu-associated repeat, incomplete penetrance",,91,618075,,"~<1/35,000",RAPGEF2,RAPGEF2,NBK535148,2018 -chr4,39348425,39348483,39350045,39350103,39318078,39318136,(AAAAG)11.8,CANVAS_RFC1,CANVAS,-,AAAAG,"AAGGG, ACAGG","CCCTT,CCTGT","AAAAG,AAAGG, AAGAG, AGAGG","CTTTT,CCTTT,CTCTT,CCTCT","AAAAA,AAAAC,AACGG,AAGAC,AAGGC,AAGGT,AGAAC,AGGGC,AGGGG,GAAAC,GGGAC,GTGAG,AAAAGA,AAAGGA,GGAAAG","TTTTT,GTTTT,CCGTT,CTTGT,CCTTG,ACCTT,CTGTT,CCCTG,CCCCT,CGTTT,CCCGT,ACCTC,CTTTTT,CCTTTT,CCCTTT","Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome",RFC1,,(AAGGG)*(ACAGG)*,AR,Intronic,Intron 2,0-11,0,11,,,,>400,400,2000,11.8,5,Typical: 36-52; Range: 19-76 (GeneReview),19,76,36,52,novel,,No information found,N/A in GeneCard,"OMIM, Cortese 2019, 30926972 (Pubmed), https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-01201-x/tables/1, s40478-021-01201-x, https://www.ncbi.nlm.nih.gov/books/NBK564656/, https://doi.org/10.1101/2023.05.12.540470","Novel, ref is AAAAG(11), path: (AAGGG)400–2000 or (ACAGG)exp","Pathogenic expansions may be flanked by other motifs. For example, (AAAGG)10-25(AAGGG)exp(AAAGG)4-6 (PMID: 32851396). Motif heterogeneity is common in unaffected individuals",58,614575,,"Unknown, <1/1,000,000",RFC1,RFC1,NBK564656,2019 -chr12,123533720,123533755,124018267,124018302,123532574,123532608,(GGC)11.7,OPDM4_RILPL1,OPDM4,-,GGC,GGC,CCG,,,,,Oculopharyngodistal myopathy type 4,RILPL1,,(GGC)*,AD,5' UTR,,9-16,9,16,,,,139 to 197,139,197,11.7,3,Typical: 18-30 (PMID: 35148830); Range: 10-30 (PMID: 35700120),10,30,18,30,ref,Protein toxic GOF,"toxic gain-of-function mechanism ",(Malacard),Yu 2022 AJHG,toxic poly-glycine protein and/or toxic RNA gain-of-function effects,,35,,,Population dependent,RILPL1,,,2022 -chr6,45422750,45422792,45390487,45390529,45257567,45257611,(GGC)15.0,CCD_RUNX2,CCD,+,GCN,GCN,CNG,,,,,Cleidocranial dysplasia,RUNX2,,(GCN)*,AD,Coding,Exon 3,<17,4,17,,,,>27,27,27,15.0,3,0 (birth) (GeneReview),0,0,0,0,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,42,119600,,"1/1,000,000 births (likely underdiagnosed)",RUNX2,RUNX2,NBK1513,1997 -chr8,118366813,118366918,119379052,119379157,119495248,119495353,(AAATA)21.6,FAME1_SAMD12,FAME1,-,TAAAA,TGAAA,ATTTC,,,"AAAAA,TAAAC,TAACA,TACAA,TACAC","TTTTT,AGTTT,ATGTT,ATTGT,AGTGT",Familial adult myoclonic epilepsy type 1,SAMD12,,(TAAAA)*(TGAAA)*(TAAAA)*,AD,Intronic,Intron 4/4,0,0,0,,,,105–3680,105,3680,21.6,5,Typical: 21-39 (PMID 29939203); Range: 12 (PMID: ...203) - 68 (PMID: 29507423),12,68,21,39,novel,RNA toxicity proposed,RNA molecules,(OMIM),Ishiura 2018. https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.27832,"Novel, pathogenic alleles include expansions of TTTTAn + TTTCAn, but only the TTTCA is specific to affected individuals, check reference and pathogenic sites with Stranger. TTTCA within TTTTA repeat region",,105,601068,,"~<1/35,000",SAMD12,SAMD12,NBK535148,2018 -chrX,140504316,140504361,139586481,139586526,138816205,138816239,(GCGGCAGCGGCGGCGG)1.9,XLMR_SOX3,XLMR,-,NGC,NGC,CNG,,,,,"X-linked panhypopituitarism ; X-linked mental retardation with isolated growth hormone ",SOX3,,(NGC)*,XR,Coding,Exon 1,< 15,15,15,,,,> 22,22,26,15.0,3,"Typical: 0-3 (PMID: 19654509, PMID: 21289259); Range: 0-9 (PMID: ...509) ",0,9,0,3,ref,Polyalanine,Polyalanine,(doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,45,300123,,,SOX3,SOX3,NBK535148,2002 -chr2,96197067,96197121,96862805,96862859,96703675,96703729,(AAAAT)11.6,FAME2_STARD7,FAME2,-,AAAAT,AAATG,ATTTC,,,"AAAAA,AAAAC,AAACC,AAACG,AAACT,AACTC,AACTG,AATAC,AATAG,ATAAC","TTTTT,GTTTT,GGTTT,CGTTT,AGTTT,AGTTG,AGTTC,ATTGT,ATTCT,ATGTT",Familial adult myoclonic epilepsy 2,STARD7,,(AAATG)*(AAAAT)*,AD,Intronic,,0,0,0,,,,>274,274,274,11.6,5,Typical: 12-30; Range: 4-60 (PMID: 31664034),4,60,12,30,novel,RNA toxicity,"RNA toxicity ",(10.1038/s41467-019-12671-y),Pathogenic Short Tandem Repeats Gnomad v3.1.2,,,54,607876,,"~<1/35,000",STARD7,STARD7,NBK535148,2019 -chr6,170561907,170562017,170870995,170871105,171935459,171935569,(GCA)37.0,SCA17_TBP,SCA17,+,GCA,GCA,AGC,,,,,Spinocerebellar ataxia type 17,TBP,,(GCA)*,AD,Coding,Exon 3,25–40,25,40,41–48,41,48,49 to 66,49,66,37.0,3,Typical: 19-48; Range: 3-62 [has second variant to delay onset] (OMIM),3,62,19,48,ref,"Polyglutamine ","Polyglutamine ",(doi.org/10.1038/nrg.2017.115) (doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK1438","Parkinson disease,late-onset",,110,607136,,"Unknown (global), 0.47:1,000,000 (Japanese)",TBP,TBP,NBK1438,1999 -chr22,19766762,19766807,19754285,19754330,20143615,20143660,,TOF_TBX1,TOF,+,GCN,GCN,CNG,,,,,Tetralogy of Fallot,TBX1,,(GCN)*,AD,Coding,,<15,15,15,,,,>25,25,25,15.0,3,0,0,0,0,0,ref,Polyalanine,Polyalanine,(OMIM),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,45,187500,,Unknown for specific gene,TBX1,TBX1,NBK535148, -chr18,55586155,55586227,53253386,53253458,55789234,55789288,(AGC)18.3,FECD3_TCF4,FECD3,-,CAG,CAG,CTG,,,,,Fuchs endothelial corneal dystrophy 3,TCF4,,(CAG)*,AD,Intronic,Intron 1,10 - 40,10,40,,,,>50,50,150,25.3,3,Typical: 40-59 (PMID: 1676829); Range: 32 (PMID: 21245398) - 70 (PMID: 25168903),32,70,40,59,ref,RNA toxicity proposed,"""sequestration of MBNL1 in RNA foci, similar to the mechanism underlying myotonic dystrophy-1 """,(10.1074/jbc.M114.621607),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,72,613267,,~4/100 (over 40),TCF4,TCF4,NBK535148,2015 -chr16,24613439,24613532,24624760,24624853,24890367,24890430,(ATTTT)12.8,FAME6_TNRC6A,FAME6,+,TTTTA,TTTCA,ATTTC,,,TTTTT,TTTTT,Familial adult myoclonic epilepsy type 6,TNRC6A,,(TTTTA)*(TTTCA)*(TTTTA)*,AD,Intronic,,0,0,0,,,,">1100, >=10, 29",1100,1100,18.8,3,"Limited clinical details from one family, ""early 20s to 70s""",23,74,23,74,novel,RNA toxicity,RNA toxicity hypothesized,(10.1038/s41588-018-0067-2),"Ishiura 2018; gnomad v3.1.2, 29507423 (Pubmed), https://doi.org/10.1038/s41597-020-00633-9, https://stripy.org/database/TNRC6A","Novel, reported pathogenic alleles: (TTTTA)22 (TTTCA)exp (TTTTA)exp, but only the TTTCA is specific to affected individuals, Alu-associated repeat. Non-pathogenic reference TTTTA repeat was expanded in nine healthy subjects 40-120 repeats and in two individuals potentially even longer (Ishiura et al., 2018).",,93,618074,,"~<1/35,000",TNRC6A,TNRC6A,NBK535148,2018 -chr16,17470907,17470922,17564764,17564779,17477910,17478013,(GCC)34.7,DBQD2_XYLT1,"DBQD2, BSS",-,GCC,GCC,CGG,,,,,Baratela-Scott Syndrome/Desbuquois dysplasia 2,XYLT1,,(GCC)*,AR,Promoter,Intron 1,<20,0,20,,,,>72,72,110,0.0,3,0 (birth),0,0,0,0,ref,Methylation,Methylation,(doi.org/10.1016/j.ajhg.2018.11.005),"LaCroix 2019, gnomad v3.1.2, 30554721",Repeat is within a sequencing missing from hg38,,1,615777,,"<1 / 1,000,000 births",XYLT1,XYLT1,NBK535148,2019 -chr3,183712188,183712222,183429976,183430010,186521657,186521706,(ATTTT)10.0,FAME4_YEATS2,FAME4,+,TTTTA,TTTCA,ATTTC,,,"TTTTT,TGTTA","TTTTT,ATGTT",Familial adult myoclonic epilepsy 4,YEATS2,,(TTTTA)*(TTTCA)*,AD,Intronic,,0,0,0,,,,>1000,1000,1000,10.0,5,Typical: 20-25 (PMID: 22713812); Range: 10-33 (PMID: 31539032),10,33,20,25,novel,RNA toxicity,RNA toxicity hypothesized,(10.1093/brain/awz267),Pathogenic Short Tandem Repeats Gnomad v3.1.2,,,34,615127,,"~<1/35,000",YEATS2,YEATS2,NBK535148,2019 -chr13,99985448,99985493,100637702,100637747,99196359,99196404,(GCG)15.3,HPE5_ZIC2,HPE5,+,GCN,GCN,CNG,,,,,Holoprosencephaly-5,ZIC2,,(GCN)*,AD,Coding,Exon 3,< 15,15,15,,,,>25,25,25,15.3,3,0,0,0,0,0,ref,"Polyalanine ","Polyalanine ",(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,45,609637,,Unknown ZIC2 specific,ZIC2,ZIC2,NBK535148,2001 -chrX,137566826,137566856,136648985,136649015,135876774,135876800,(CGC)9.0,VACTERLX_ZIC3,VACTERLX,+,GCN,GCN,CNG,,,,,X-linked VACTERL syndrome,ZIC3,,(GCN)*,XR,Coding,,<10,9,10,11,11,11,>12,12,12,9.0,3,0,0,0,0,0,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,30,314390,,Unknown,ZIC3,ZIC3,NBK535148, -chr7,55887601,55887639,55955294,55955332,56047901,56047939,(GCG)15.0,FRA7A_ZNF713,FRA7A,+,GCG,GCG,CGG,,,,,Autism spectrum disorder associated with fragile site FRA7A,ZNF713,,(GCG)*,AD,Intronic,,5-22,5,22,85,85,85,450,450,450,13.0,3,2-3 (four individuals; PMID: 25196122),2,3,2,3,ref,Methylation,Methylation,(OMIM),"OMIM, https://pubmed.ncbi.nlm.nih.gov/25196122/",,,38,616181,,,,,, -chr3,129172577,129172659,128891420,128891502,131917483,131917557,(CAGG)18.8,DM2_CNBP,DM2,-,CAGG,CAGG,CCTG,,,,,Myotonic Dystrophy Type 2,CNBP,(CAGG)n(CAGA)10(CA)19,(CAGG)*(CAGA)*(CA)*,AD,Intronic,,11–26,11,26,27-74,27,74,"75-11,000",75,11000,20.8,4,Typical: 28-56 (PMID: 29086017); Range: 0-73 (PMID: 31159885),0,73,28,56,ref,Aberrant splicing,Aberrant splicing,(doi.org/10.1093/hmg/ddr568),"Hannan 2018, Mirkin 2007, GeneReviews NBK1466, https://doi.org/10.1038/s41580-021-00382-6",(TG)n(TCTG)n(CCTG)n. CCTG expansion causes DM2 but the other repeat units are also variable.,,82,602668,,"2.29/100,000",CNBP,CNBP,NBK1466,2001 -chr21,43776443,43776479,45196324,45196360,42132055,42132091,,EPM1_CSTB,EPM1,-,CGCGGGGCGGGG,CGCGGGGCGGGG,CCCCGCCCCGCG,,,,,Progressive Myoclonic Epilepsy Type 1 (EPM1) Unverricht-Lundborg Disease (ULD),CSTB,,(CGCGGGGCGGGG)*,AR,Promoter,,2-3,2,3,12-17,12,17,>=30,30,81,,12,Typical: 6-15 (GeneReview); Range: 6-16 (PMID: 9012407),6,16,6,15,,,,,"OMIM, https://www.ncbi.nlm.nih.gov/books/NBK1142/, PMID: 9126745",,,,254800,,,,CSTB,NBK1142,1997 -chr17,80147059,80147139,78120858,78120938,81047454,81047534,,RCPS_EIF4A3,RCPS,-,CCTCGCTGTGCCGCTGCCGA,CCTCGCTGTGCCGCTGCCGA,ACAGCGAGGTCGGCAGCGGC,,,,,Richieri-Costa-Pereira syndrome,EIF4A3,,(CCTCGCTGCGCCGCTGCCGA)*(CCTCGCTGTGCCGCTGCCGA)*,AR,5'UTR,,1-9,1,9,10-13,10,13,>14,14,16,,20,0 (birth),0,0,0,0,,,,,https://www.ncbi.nlm.nih.gov/books/NBK535148/,,,,268305,,,,EIF4A3,NBK535148, -chr20,4699397,4699493,4680043,4680139,4738633,4738705,,CJD_PRNP,CJD,+,GGTGGTGGCTGGGGGCAGCCTCAT,CCTCATGGTGGTGGCTGGGGGCAG,AGCCTCATGGTGGTGGCTGGGGGC,,,,,Creutzfeldt-Jakob disease,PRNP,(CCTCAGGGCGGTGGTGGCTGGGGGCAG)1(CCTCATGGTGGTGGCTGGGGGCAG)n,(CCTCAGGGCGGTGGTGGCTGGGGGCAG)*(CCTCATGGTGGTGGCTGGGGGCAG)*,AD,Coding,Exon 2,<=4,,4,,,,>=5,5,,,24,Typical: 50-60 (GeneReview); Range: 31-63 (PMID: 37379724),31,63,50,60,,,,,https://www.ncbi.nlm.nih.gov/books/NBK1229/,,,,123400,,,,PRNP,NBK1229, -chr1,1435798,1435818,1371178,1371198,870158,870178,,HMNR7_VWA1,HMNR7,+,GGCGCGGAGC,GGCGCGGAGC,AGCGGCGCGG,,,,,"Neuronopathy, distal hereditary motor, autosomal recessive 7",VWA1,,(GGCGCGGAGC)*,AR,Coding,Exon 1,2,2,2,,,,Any deviation from 2,1,3,,10,Typical: 1-3 (PMID: 33559681); Range: 0-10 (OMIM),0,10,1,3,,,,,,,Any deviation from 2 motifs is thought to be pathogenic,,619216,,,,VWA1,NBK535148, -chr1,94418422,94418444,94883978,94884000,94266545,94266567,,OPDM_ABCD3,OPDM,+,GCC,GCC,CCG,,,,,Oculopharyngodistal myopathy,ABCD3,,(GCC)*,AD,5'UTR,,3-44,3,44,,,,118-694,118,694,7.7,3,"Typical: 24-30, 10-50 (doi.org/10.1101/2023.10.09.23296582)",10,50,24,30,,,,,https://doi.org/10.1101/2023.10.09.23296582,,,,,,,,,,2023 -chr13,102161577,102161726,102813927,102814076,101377640,101377789,,SCA27B_FGF14,SCA27B,-,AAG,AAG,CTT,,,,,Spinocerebellar ataxia 27B,FGF14,,(AAG)*,AD,Intronic,Intron 1,8-249,8,249,250-299,250,299,>300,300,637,50.3,3,Typical: 42-70; Range: 21-87 (NBK599589),21,87,42,70,ref,Haploinsufficiency,Reduced transcript 2,PMCID: PMC10042577,"https://www.omim.org/entry/620174, https://www.cell.com/ajhg/fulltext/S0002-9297(22)00506-7, PMCID: PMC10042577, PMID: 37399286","250-300 pathogenic with incomplete penetrance, >300 complete penetrance",,,620174,,,FGF14,,NBK599589,2023 -chr16,72787695,72787758,72821594,72821657,78605503,78605569,(GCC)22.3,SCA4_ZFHX3,SCA4,-,GCC,GCC,CGG,,,,,Spinocerebellar ataxia 4,ZFHX3,,(GCC)*,AD,Coding,Last Exon,16-26 (majority 21),16,26,,,,46-64,46,64,21.3,3,"Typical: 37- 56; Range: 15 - 60 (PMID: 38035881 - https://doi.org/10.1101/2023.10.03.23296230) ",15,60,37,56,ref,,,,https://doi.org/10.1101/2023.10.03.23296230,,Expansion found in affected individuals from 3 families and not in any of the 1001 controls,,600223,,,,,,2023 -chr16,67842863,67842950,67876766,67876853,73638637,73638724,,SCA_THAP11,SCA,+,CAG,CAG,AGC,,,,,Spinocerebellar ataxia,THAP11,,(CAG)*,AD,Coding,Exon 1,20-38,20,38,,,,45-100,45,100,29.3,3,Typical: 8-40; Range: 4-51 (PMID: 37148549),4,51,8,40,ref,PolyQ toxicity,,https://doi.org/10.1002/mds.29412,"https://doi.org/10.1002/mds.29412, https://doi.org/10.1042/ETLS20230018",,"Expansion found in affected individuals from 2 families and not in 500 controls. Longer alleles were associated wither earlier age of onset. For example, an individual with 100 repeats had age of onset at 4 years.",,,,,,,,2023 +chrX,25013649,25013697,25031766,25031814,24597886,24597934,(GCC)14.7,EIEE1_ARX,EIEE1,-,NGC,NGC,CNG,,,,,Early-infantile epileptic encephalopathy,ARX,,(NGC)*,XR,Coding,Exon 2,10-16,10,16,,,,17-27,17,27,14.7,3,"Typical: 0 (PMID: 21204215, PMID: 9307258, OMIM); Range: 0-4 (Childhood epilepsy, cognitive disability, ∼70% of cases infantile spasms --> seizures by 3 or 4 years re: PMID: 19587282)",0,4,0,0,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"GeneReviews NBK535148, OMIM",Exon 2 aa 110-115,,43,308350; 300419; 300215,,Unknown,ARX_1,ARX_1,NBK535148, +chrX,25013530,25013565,25031647,25031682,24597767,24597799,(GGCCGCGGCGGCCGC)2.2,PRTS_ARX,PRTS,-,NGC,NGC,CNG,,,,,Partington syndrome,ARX,,(NGC)*,XR,Coding,Exon 2,12,12,12,,,,20,20,20,12.0,3,Typical: 1-3; Range: 0-4 (OMIM); Mildness can make diagnosis difficult (particularly mild/absent in females) ,0,4,1,3,ref,Polyalanine,Polyalanine,(OMIM) (doi.org/10.1007/s11604-022-01343-5),"GeneReviews NBK535148, OMIM","Novel, Exon 2 aa 144-155",,35,309510,,Unknown,ARX_2,ARX_2,NBK535148, +chr22,45795355,45795424,46191235,46191304,46280060,46280129,(ATTCT)15.0,SCA10_ATXN10,SCA10,+,ATTCT,ATTCT,ATTCT,,,,,Spinocerebellar Ataxia Type 10,ATXN10,,(ATTCT)*,AD,Intronic,Intron 9/11,10–32,10,32,280-850,280,850,800-4500,800,4500,14.0,5,Typical: 12-48; Range: 11-83 (NBK1175),11,83,12,48,ref,Unknown,Transdominant mechanism theorized,(malacard),"Hannan 2018, Mirkin 2007, GeneReviews NBK535148, s40478-021-01201-x",Interruptions: ATCCT,,69,603516,,Unknown; >300 individuals (GeneReview),ATXN10,ATXN10,,2000 +chr16,66490397,66490466,66524300,66524369,72284667,72284761,(AATAA)19.4,SCA31_BEAN1,SCA31,+,AATAA,"TGGAA,TAGAA","AATGG,AATAG",,,"AAAAA,AAAAC,AAATG,AGAAA,ATAAG,TAAAC,TAACA,TACAA,TCAAA,TGCAA","AAAAA,AAAAC,AAATG,AAAAG,AAGAT,AAACT,AACAT,AATAC,AAATC,AATGC",Spinocerebellar Ataxia Type 31,BEAN1,,(TGGAA)*(TAGAA)*,AD,Intronic,Intron 4/4,0-10,0,10,,,,>110,110,760,14.4,5,Typical: 56-62 (PMID: 36563608); Range: 8-83 (PMID: 23331413) ,8,83,56,62,novel,Epigenetic,Role in heterochromatin or chromosomal structure theorized ,(OMIM),"OMIM, Sato 2009, 19878914 (Pubmed), https://doi.org/10.1038/s41580-021-00382-6","Novel, STR-containing insertion, not present in reference genome: Reds disagree on normal/pathogenic sizes",,69,117210,,Unknown (more common in Japanese pop),BEAN1,BEAN1,NBK535148,2009 +chr9,27573484,27573546,27573482,27573544,27584063,27584155,(GCCCCG)15.8,FTDALS1_C9orf72,FTDALS1,-,GGCCCC,GGCCCC,CCGGGG,,,,,Frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS),C9orf72,,(GGCCCC)*,AD,Intronic,Intron 1 or 5' depending on transcript,3–25 (2-19 Reds),2,20,20-60,20,60,250-2000,250,2000,10.8,6,Typical: 50-64; Range: 20-91 (GeneReview),20,91,50,64,ref,RNA toxicity proposed,"""The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA/DNA hybrids (R-loops). The structural polymorphism causes a repeat length-dependent accumulation of transcripts aborted in the HRE region.""",OMIM,"Hannan 2018, GeneReviews NBK535148, OMIM, s40478-021-01201-x",,,62,105500,,"The expansion of a hexanucleotide repeat GGGGCC in C9orf72 is the most common known cause of ALS accounting for ~ 40% familial cases and ~ 7% sporadic cases in the European population; overall ALS incidence is 1-2/100,000 person-years, point prevalence is 3-5/100,000 (Europe/US); lifetime risk is 1 in 300 (PMID: 31315673). C9orf72-FTD is estimated to be 0.04-134:100,000 (GeneReview), and by our estimates 0.65-1.56/100,000 for C9orf72-ALS. ",C9ORF72,C9ORF72,NBK268647,2011 +chr11,119206289,119206322,119076999,119077032,119226663,119226696,(CGG)11.3,JBS_CBL,JBS,+,CGG,CGG,CGG,,,,,Jacobsen syndrome (FRAX11B fragile site),CBL,,(CGG)*,AD,5' UTR,,<79,11,79,,,,>100,100,100,11.3,3,Condition at birth.,0,0,,,ref,,No information found,(OMIM),"https://doi.org/10.1038/s41580-021-00382-6, 7603564 (PubMed)",,,33,147791,,"1/100,000 births; female/male ratio 2:1 (PMID: 19267933); expansion can lead to deletion (shown in 2 cases) but total causality is unclear",CBL,,, +chr19,18786034,18786049,18896844,18896859,18921630,18921645,,EDM1-PSACH_COMP,"EDM1, PSACH",-,GTC,GTC,ACG,,,,,"Multiple epiphyseal dysplasia, Pseudoachondroplasia",COMP,,(GTC)*,AD,Coding,,5,5,5,,,,4 or 6-7,6,7,5.0,3,Typical: 0-2 (COMP-PSACH)/ 1-12 (EDM1); Range: 0 (PSACH) - 13 (EDM1),0,13,0,12,ref,Protein LOF,"LOF, domain dependent",(https://pubmed.ncbi.nlm.nih.gov/29530484/),Pathogenic Short Tandem Repeats Gnomad v3.1.2,"Two diseases, same locus. Both expansions and contractions associated with disease",,15,132400; 177170,,"Specific contribution of COMP repeats to EDM1 is unknown (~300 COMP mutation variants for both phenotypes); likely 1:90,000 prevalence for COMP-PSACH that is repeat-specific.",COMP,COMP,NBK1123; NBK1487, +chr1,57367044,57367125,57832716,57832797,57245936,57245977,(AAAAT)8.6,SCA37_DAB1,SCA37,-,AAAAT,GAAAT,ATTTC,,,AAAAA,TTTTT,Spinocerebellar Ataxia Type 37,DAB1,,(AAAAT)*(GAAAT)*(AAAAT)*,AD,Intronic,Intron 1 (most isoforms),0-16,0,16,,,,31-75,31,75,16.6,5,Typical: 33-53; Range: 18-64 (GeneReview),18,64,33,53,novel,Protein toxic GOF,toxic gain-of-function mechanism,(OMIM),"Seixas et al 2017 AJHG, NBK541729, s40478-021-01201-x","Novel. Normal: [(ATTTT)7–400] Pathogenic: [(ATTTT)60–79(ATTTC)31–75(ATTTT)58–90], ATTTC within (ATTTT)7–400 repeat region",,81,615945,,"0.20/100,000 specific to Portugal; not yet found in other geographic regions",DAB1,DAB1,NBK541729,2017 +chr12,50505002,50505022,50898785,50898805,50468096,50468116,,FRA12A_DIP2B,FRA12A,+,GGC,GGC,CGG,,,,,"Intellectual developmental disorder, FRA12A type",DIP2B,,(GGC)*,AD,5' UTR,,6-23,6,23,~139-206,139,206,~273-306,273,306,7.0,3,Typical: 0-1 (PMID: 3742859); Range: 0-3 (PMID: 4042396),0,3,0,1,ref,"Increased gene expression, methylation","Increased gene expression, methylation","(OMIM, https://www.medrxiv.org/content/10.1101/2022.09.12.22279739v3.full-text)","OMIM, NBK535148, https://www.medrxiv.org/content/10.1101/2022.09.12.22279739v3.full-text",,,20,136630,,,DIP2B,DIP2B,NBK535148, +chr19,14496041,14496074,14606853,14606886,14622656,14622702,(CCG)15.7,OPDM2_GIPC1,OPDM2,-,CCG,CCG,CGG,,,,,Oculopharyngodistal myopathy,GIPC1,,(CCG)*,AD,5' UTR,Exon 1,6-29,6,29,,,,70-138,70,138,14.7,3,Typical: 20-34 (PMID: 32413282); Range: 14 (PMID: ...282) - 70 (PMID: 33374016),14,70,20,34,ref,RNA toxicity,RNA mediated toxicity hypothesized; unknown,"(OMIM), (doi.org/10.1007/s11604-022-01343-5)","Pathogenic Short Tandem Repeats Gnomad v3.1.2, 32413282 (Pubmed)",,,33,618940,,Population dependent; presumed rare.,GIPC1,GIPC1,NBK535148,2020 +chr2,190880873,190880920,191745599,191745646,191369983,191370024,(GCA)14.0,GDPAG_GLS,GDPAG,+,GCA,GCA,AGC,,,,,Glutaminase deficiency,GLS,,(GCA)*,AR,5' UTR,Exon 1,5-26,5,26,,,,90 - 1500,90,1500,16.0,3,"Early childhood (2-4; PMID: 30970188, 35913761)",2,4,2,4,ref,"Decreased gene expression, methylation",Change in histone modification decreases transcription,(OMIM),"van Kuilenburg 2019 NEJM, 30970188 (Pubmed)",Several compound het cases reported,,47,618412,,"As of 2019, only 7 cases total of GLS deficiency, including non-repeat",GLS,GLS,NBK535148,2019 +chr7,27199678,27199732,27239297,27239351,27335815,27335849,(GCCGCGGCCGCCGCCG)1.9,HFG_HOXA13-III,HFG-III,-,NGC,NGC,CNG,,,,,Hand-foot-genital syndrome 3,HOXA13,,(NGC)*,AD,Coding,Exon 1,8-18,8,18,,,,24-32,24,32,18.0,3,0 (birth),0,0,0,0,ref,Polyalanine ,Polyalanine ,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK1423",There are 3 pathogenic polyalanine tracts in this gene,,54,140000,,"""Extremely rare"" (GeneReview)",HOXA13_3,HOXA13_3,NBK1423,2000 +chr7,27199825,27199861,27239444,27239480,27335914,27335954,(GCAGCCGCCGCCGCT)2.9,HFG_HOXA13-II,HFG-II,-,NGC,NGC,CNG,,,,,Hand-foot-genital syndrome 2,HOXA13,,(NGC)*,AD,Coding,Exon 1,12,12,12,,,,18,18,18,12.0,3,0 (birth),0,0,0,0,ref,Polyalanine ,Polyalanine ,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK1423",There are 3 pathogenic polyalanine tracts in this gene,,36,140000,,"""Extremely rare"" (GeneReview)",HOXA13_2,HOXA13_2,NBK1423,2000 +chr7,27199924,27199966,27239543,27239585,27335920,27335951,(GCAGCCGCCGCCGCT)2.7,HFG_HOXA13-I,HFG-I,-,NGC,NGC,CNG,,,,,Hand-foot-genital syndrome 1,HOXA13,,(NGC)*,AD,Coding,Exon 1,14,14,14,,,,22,22,22,14.0,3,0 (birth),0,0,0,0,ref,Polyalanine ,Polyalanine ,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats, Gnomad v3.1.2, NBK1423",There are 3 pathogenic polyalanine tracts in this gene,,42,140000,,"""Extremely rare"" (GeneReview)",HOXA13_1,HOXA13_1,NBK1423,2000 +chr2,176093058,176093103,176957786,176957831,176581179,176581220,(GGC)14.0,SD5_HOXD13,SD5,+,GCN,GCN,CNG,,,,,Syndactyly,HOXD13,,(GCN)*,AD,Coding,Exon 1,< 15,14,15,,,,>22,22,22,14.0,3,0 (birth),0,0,0,0,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,45,186000,,3 individuals (GeneReview),HOXD13,HOXD13,NBK535148,1996 +chr16,87604283,87604329,87637889,87637935,93675724,93675776,(GCT)17.3,HDL2_JPH3,HDL2,+,CTG,CTG,CTG,,,,,Huntington disease-like 2,JPH3,,(CTG)*,AD,Coding,Exon 2,6–28,6,28,29-39,29,39,40–58,40,58,15.6667,3,Typical: 30-52; Range: 12-66 (GeneReview),12,66,30,52,ref,,"""unstable vertical transmission""",(doi.org/10.1007/s11604-022-01343-5),"Hannan 2018, Mirkin 2007, GeneReviews NBK1529",reflen + pos from HipSTR,,46,606438,,"<1/1,000,000 (Orphanet); largely in individuals of African descent",JPH3,JPH3,NBK1529,2001 +chr8,104588972,104588999,105601200,105601227,105716410,105716441,(CGC)10.7,OPDM1_LRP12,OPDM1,-,CGC,CGC,CGG,,,,,Oculopharyngodistal myopathy type 1,LRP12,,(CGC)*,AD,5' UTR,,13-45,13,45,,,,90,90,90,11.7,3,Typical: 31-51 (PMID: 34047774); Range: 7-66 (PMID: 2124290),7,66,31,51,ref,RNA toxicity,RNA mediated toxicity hypothesized; unknown,"(OMIM), (doi.org/10.1007/s11604-022-01343-5)","OMIM 164310, Ishiura et al [2019], Ehdn, NBK535148, PMID 31332380",CGG/CGT,,27,164310,,Population dependent; unknown percentage of LRP12 pathogenic variants.,LRP12,LRP12,NBK535148,2019 +chr5,10356339,10356411,10356451,10356523,10295521,10295593,(TTTTA)14.8,FAME3_MARCHF6,FAME3,+,TTTTA,TTTCA,ATTTC,,,"ATGTT,TAGTT,TTTTG,TTTTT","ATGTT,AGTTT,GTTTT,TTTTT",Familial adult myoclonic epilepsy type 3,MARCHF6,,(TTTTA)*(TTTCA)*,AD,Intronic,Intron 1,0,,,,,,"791-1,035 repeats",791,1035,14.8,5,Typical: 24-41 (PMID: 19616813); Range: 10 (OMIM) - 46 (PMID: 31664039),10,46,24,41,novel,Unknown,Noted as unknown in literature,(OMIM),"Florian, R.T. Nat Comm. 2019",TTTTA + TTTCA,,72,613608,,"Overall FAME prevalence is < 1/35,000; MARCHF6-caused much smaller",MARCHF6,MARCHF6,NBK535148,2019 +chr15,22786677,22786701,23086366,23086390,20458505,20458536,(GCG)10.7,ALS1_NIPA1,ALS1,+,GCG,GCG,CGG,,,,,Amyotrophic lateral sclerosis,NIPA1,,(GCG)*,AD,Coding,,6-10,6,10,,,,> 11,11,56,10.7,3,Typical: 44-60 (PMID: 26777436); Range: 25 (PMID: 22378146) - 77 (PMID: 26777436),25,77,44,60,ref,,No information found,N/A in GeneCard,"Pathogenic Short Tandem Repeats Gnomad v3.1.2, 30342764 (Pubmed), path range from gnomAD",Proposed modifier for ALS,,24,105400,,"2.7-7.4/100,000 (All ALS, not just this locus), NIPA1 + C9orf72 is 0.37% of ALS patients; frequency of NIPA1 expansion in controls is 3.74% (PMID: 31286297)",NIPA1,NIPA1,, +chr20,2652733,2652757,2633379,2633403,2683200,2683224,(GCCTGG)8.8,SCA36_NOP56,SCA36,+,GGCCTG,GGCCTG,CCTGGG,,,,,Spinocerebellar ataxia type 36,NOP56,(GGCCTG)n(CGCCTG)3,(GGCCTG)*(CGCCTG)*,AD,Intronic,Intron 1,3 to 14,3,14,15-649,15,649,650-2500,650,2500,7.2,6,Typical: 40-60 (GeneReview); Range: 28 (PMID: 37810464) - 67 (PMID: 37332636),28,67,40,60,ref,Protein toxic GOF,toxic gain-of-function mechanism,(OMIM),"GeneReviews, OMIM, NBK231880",,,42,614153,,Western Japan: 3.6% of all SCA; Costa da Morte region of Spain: 6.3% of all SCA(PMID: 37332636); US: 0.7% of large undiagnosed ataxia cohort (PMID: 28761930),NOP56,NOP56,,2011 +chr1,149390803,149390842,145209324,145209354,148519696,148519738,(GGC)14.3,NIID_NOTCH2NLC,NIID,+,GGC,GGC,CGG,,,,,"Neuronal intranuclear inclusion disease, Alzheimer disease and parkinsonism phenotype",NOTCH2NLC,,(GGC)*,AD,5' UTR,5' Region,7–39,7,39,,,,66-517,66,517,13.3,3,Typical: 30-70 (OMIM); Range: 10 (PMID: 37090934) - 78 (PMID: 37305750),10,78,30,70,ref,Unknown,May relate to methylation or RNA pathogenicity; Unknown,(OMIM) (doi.org/10.1007/s11604-022-01343-5),"doi: 10.1038/s41588-019-0458-z, https://doi.org/10.1016/j.ajhg.2019.05.013, s40478-021-01201-x","May be issues with parology between genes: C253572.1, NOTCH2, NOTCH2NL, NBPF14, NBPF19 ?? Motif variation in controls: (AGG)(CGG)n(AGG)0-3(CGG)0-2. Methylation involved",Age of onset inversely related to allele size (PMID: 38377026),39,603472,,>400 patients reported in literature (PMID: 37371433),NOTCH2NLC,NOTCH2NLC,NBK535148,2019 +chr10,79826383,79826404,81586139,81586160,80695712,80695748,(GCG)12.7,OPML1_NUTM2B-AS1,OPML1,+,GGC,GGC,CGG,,,,,Oculopharyngeal myopathy with leukoencephalopathy 1,NUTM2B-AS1,,(GGC)*,AD,lncRNA,Exon 1 (noncoding),3-16,3,16,,,,>700,700,700,7.0,3,15-40 (PMID: 31332380; only characterized in one family),15,40,15,40,ref,RNA toxicity,"RNA mediated toxicity hypothesized, unknown",(OMIM) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, Ishiura 2019, doi: 10.1038/s41588-019-0458-z, https://doi.org/10.1038/s41580-021-00382-6","Not in TRF annotation, alt transcript in opposite direction: LOC642361",,21,618637,,"""Rare""",NUTM2B-AS1,NUTM2B-AS1,NBK535148,2019 +chr15,89333589,89333629,89876820,89876860,87088412,87088452,(GCT)13.7,CPEO_POLG,CPEO,-,GCT,GCT,AGC,,,,,"Progressive external ophthalmoplegia, Parkinson’s disease",POLG,,(CTG)*TTG(CTG)*,,,,10,10,10,,,,Deviation from 10 may impart disease risk with variable penetrance,,,13.7,3,Typical: 57 (PMID: 20399836) - 59 (PMID: 20826197); Range: 23-87 (PMID: 20399836),23,87,57,59,ref,,No information found,N/A in GeneCard,"PMC2905783, PMID: 20399836, PMID: 10196696",Unconfirmed association,There is conflicting evidence for the association between this repeat expansion and Parkinson's risk (PMID: 20399836 and PMID: 10196696). Deviation from 10 may impart disease risk with variable penetrance. May be predisposing factor in earlier age of onset in FRDA patients (PMID: 19043662),40,Disease association unclear,,Unknown,,,, +chr5,146878728,146878759,146258291,146258322,147414734,147414765,(GCT)15.7,SCA12_PPP2R2B,SCA12,-,GCT,GCT,AGC,,,,,Spinocerebellar ataxia type 12,PPP2R2B,,(GCT)*,AD,Promoter,,4–32,4,32,,,,51–78,51,78,10.7,3,Typical: 26-50; Range: 8-56 (OMIM),8,56,26,50,ref,Unknown,Noted as unknown in literature,"N/A in GeneCard,","Hannan 2018, Mirkin 2007, OMIM, NBK535148, s40478-021-01201-x",(Roda et al. suggested that the ATXN8 or ATXN8OS gene should not be evaluated in isolation as a candidate gene for spinocerebellar degenerative disease),,31,604326,,Unknown. Frequent in India; rare in other places (PMID: 34711523),PPP2R2B,PPP2R2B,NBK535148,1999 +chr9,130681606,130681639,133556993,133557026,142886569,142886595,(CGC)9.0,HSAN-VIII_PRDM12,HSAN VIII,+,GCC,GCC,CCG,,,,,Hereditary sensory and autonomic neuropathy type VIII,PRDM12,,(GCC)*,AR,Coding,Exon,<14,12,14,,,,>18,18,19,12.0,3,0 (birth),0,0,0,0,ref,"LOF, epigenetic","""mutations abrogated the histone-modifying potential of PRDM12, consistent with a loss of function""",OMIM,"Pathogenic Short Tandem Repeats Gnomad v3.1.2, https://doi.org/10.1038/ng.3308",,,33,616488,,"Found in 2 families. All PRDM12 disease mutations < 1/1,000,000",PRDM12,PRDM12,NBK535148, +chr4,159342527,159342618,160263679,160263770,162693304,162693405,(TTTTA)20.4,FAME7_RAPGEF2,FAME7,+,TTTTA,TTTCA,ATTTC,,,"TTTTT,TTATG","TTTTT,ATGTT",Familial adult myoclonic epilepsy type 7,RAPGEF2,,(TTTTA)*(TTTCA)*(TTTTA)*,AD,Intronic,Intron 14,0-1,0,1,,,,>=60,60,60,17.4,5,Typical: 20-33 (PMID: 30351492); Range: 18 (PMID: 29507423) - 37 (PMID: 30351492),18,37,20,33,novel,RNA toxicity,RNA toxicity hypothesized,(10.1038/s41588-018-0067-2),"Ishiura 2018, 29507423 (Pubmed), https://sci-hub.hkvisa.net/10.1111/ene.13848","Novel, (TTTTA)exp(TTTCA)exp(TTTTA)n, but only the TTTCA is specific to affected individuals, Alu-associated repeat, incomplete penetrance",,91,618075,,"FAME overall is 1/35,000 in Japan",RAPGEF2,RAPGEF2,NBK535148,2018 +chr4,39348425,39348483,39350045,39350103,39318078,39318136,(AAAAG)11.8,CANVAS_RFC1,CANVAS,-,AAAAG,"AAGGG, ACAGG","CCCTT,CCTGT","AAAAG,AAAGG, AAGAG, AGAGG","CTTTT,CCTTT,CTCTT,CCTCT","AAAAA,AAAAC,AACGG,AAGAC,AAGGC,AAGGT,AGAAC,AGGGC,AGGGG,GAAAC,GGGAC,GTGAG,AAAAGA,AAAGGA,GGAAAG","TTTTT,GTTTT,CCGTT,CTTGT,CCTTG,ACCTT,CTGTT,CCCTG,CCCCT,CGTTT,CCCGT,ACCTC,CTTTTT,CCTTTT,CCCTTT","Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome",RFC1,,(AAGGG)*(ACAGG)*,AR,Intronic,Intron 2,0-11,0,11,,,,>400,400,2000,11.8,5,Typical: 36-52; Range: 19-76 (GeneReviews),19,76,36,52,novel,,No information found,N/A in GeneCard,"OMIM, Cortese 2019, 30926972 (Pubmed), https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-021-01201-x/tables/1, s40478-021-01201-x, https://www.ncbi.nlm.nih.gov/books/NBK564656/, https://doi.org/10.1101/2023.05.12.540470","Novel, ref is AAAAG(11), path: (AAGGG)400–2000 or (ACAGG)exp","Pathogenic expansions may be flanked by other motifs. For example, (AAAGG)10-25(AAGGG)exp(AAAGG)4-6 (PMID: 32851396). Motif heterogeneity is common in unaffected individuals",58,614575,,"Carrier frequency in European is 0.7-4% and in Chinese Han population is 2.24%; estimated prevalence of 1/20,000 to 1/625 (GeneReview)",RFC1,RFC1,NBK564656,2019 +chr12,123533720,123533755,124018267,124018302,123532574,123532608,(GGC)11.7,OPDM4_RILPL1,OPDM4,-,GGC,GGC,CCG,,,,,Oculopharyngodistal myopathy type 4,RILPL1,,(GGC)*,AD,5' UTR,,9-16,9,16,,,,139 to 197,139,197,11.7,3,Typical: 18-30 (PMID: 35148830); Range: 10-30 (PMID: 35700120),10,30,18,30,ref,Protein toxic GOF,toxic gain-of-function mechanism ,(Malacard),Yu 2022 AJHG,toxic poly-glycine protein and/or toxic RNA gain-of-function effects,,35,,,Population dependent. 21.6% of one OPDM cohort (PMID: 35148830),RILPL1,,,2022 +chr6,45422750,45422792,45390487,45390529,45257567,45257611,(GGC)15.0,CCD_RUNX2,CCD,+,GCN,GCN,CNG,,,,,Cleidocranial dysplasia,RUNX2,,(GCN)*,AD,Coding,Exon 3,<17,4,17,,,,>27,27,27,15.0,3,0 (birth) (GeneReviews),0,0,0,0,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977) (doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,42,119600,,"All conditions 1/1,000,000 births (likely underdiagnosed); Utah population frequency 0.12/10,000",RUNX2,RUNX2,NBK1513,1997 +chr8,118366813,118366918,119379052,119379157,119495248,119495353,(AAATA)21.6,FAME1_SAMD12,FAME1,-,TAAAA,TGAAA,ATTTC,,,"AAAAA,TAAAC,TAACA,TACAA,TACAC","TTTTT,AGTTT,ATGTT,ATTGT,AGTGT",Familial adult myoclonic epilepsy type 1,SAMD12,,(TAAAA)*(TGAAA)*(TAAAA)*,AD,Intronic,Intron 4/4,0,0,0,,,,105–3680,105,3680,21.6,5,Typical: 21-39 (PMID: 29939203); Range: 12 (PMID: 29939203) - 68 (PMID: 29507423),12,68,21,39,novel,RNA toxicity proposed,RNA molecules,(OMIM),Ishiura 2018. https://movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.27832,"Novel, pathogenic alleles include expansions of TTTTAn + TTTCAn, but only the TTTCA is specific to affected individuals, check reference and pathogenic sites with Stranger. TTTCA within TTTTA repeat region",,105,601068,,"FAME overall is 1/35,000 in Japan",SAMD12,SAMD12,NBK535148,2018 +chrX,140504316,140504361,139586481,139586526,138816205,138816239,(GCGGCAGCGGCGGCGG)1.9,XLMR_SOX3,XLMR,-,NGC,NGC,CNG,,,,,X-linked panhypopituitarism ; X-linked mental retardation with isolated growth hormone ,SOX3,,(NGC)*,XR,Coding,Exon 1,< 15,15,15,,,,> 22,22,26,15.0,3,"Typical: 0-3 (PMID: 19654509, PMID: 21289259); Range: 0-9 (PMID: 19654509) ",0,9,0,3,ref,Polyalanine,Polyalanine,(doi.org/10.1007/s11604-022-01343-5),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,45,300123,,3 families.,SOX3,SOX3,NBK535148,2002 +chr2,96197067,96197121,96862805,96862859,96703675,96703729,(AAAAT)11.6,FAME2_STARD7,FAME2,-,AAAAT,AAATG,ATTTC,,,"AAAAA,AAAAC,AAACC,AAACG,AAACT,AACTC,AACTG,AATAC,AATAG,ATAAC","TTTTT,GTTTT,GGTTT,CGTTT,AGTTT,AGTTG,AGTTC,ATTGT,ATTCT,ATGTT",Familial adult myoclonic epilepsy 2,STARD7,,(AAATG)*(AAAAT)*,AD,Intronic,,0,0,0,,,,>274,274,274,11.6,5,Typical: 12-30; Range: 4-60 (PMID: 31664034),4,60,12,30,novel,RNA toxicity,RNA toxicity ,(10.1038/s41467-019-12671-y),Pathogenic Short Tandem Repeats Gnomad v3.1.2,,,54,607876,,"FAME overall is 1/35,000 in Japan",STARD7,STARD7,NBK535148,2019 +chr22,19766762,19766807,19754285,19754330,20143615,20143660,,TOF_TBX1,TOF,+,GCN,GCN,CNG,,,,,Tetralogy of Fallot,TBX1,,(GCN)*,AD,Coding,,<15,15,15,,,,>25,25,25,15.0,3,0,0,0,0,0,ref,Polyalanine,Polyalanine,(OMIM),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,45,187500,,1 individual with STR mutation (GeneReview),TBX1,TBX1,NBK535148, +chr16,24613439,24613532,24624760,24624853,24890367,24890430,(ATTTT)12.8,FAME6_TNRC6A,FAME6,+,TTTTA,TTTCA,ATTTC,,,TTTTT,TTTTT,Familial adult myoclonic epilepsy type 6,TNRC6A,,(TTTTA)*(TTTCA)*(TTTTA)*,AD,Intronic,,0,0,0,,,,">1100, >=10, 29",1100,1100,18.8,3,"Limited clinical details from one family, ""early 20s to 70s""",23,74,23,74,novel,RNA toxicity,RNA toxicity hypothesized,(10.1038/s41588-018-0067-2),"Ishiura 2018; gnomad v3.1.2, 29507423 (Pubmed), https://doi.org/10.1038/s41597-020-00633-9, https://stripy.org/database/TNRC6A","Novel, reported pathogenic alleles: (TTTTA)22 (TTTCA)exp (TTTTA)exp, but only the TTTCA is specific to affected individuals, Alu-associated repeat. Non-pathogenic reference TTTTA repeat was expanded in nine healthy subjects 40-120 repeats and in two individuals potentially even longer (Ishiura et al., 2018).",,93,618074,,"FAME overall is 1/35,000 in Japan",TNRC6A,TNRC6A,NBK535148,2018 +chr16,17470907,17470922,17564764,17564779,17477910,17478013,(GCC)34.7,DBQD2_XYLT1,"DBQD2, BSS",-,GCC,GCC,CGG,,,,,Baratela-Scott Syndrome/Desbuquois dysplasia 2,XYLT1,,(GCC)*,AR,Promoter,Intron 1,<20,0,20,,,,>72,72,110,0.0,3,0 (birth),0,0,0,0,ref,Methylation,Methylation,(doi.org/10.1016/j.ajhg.2018.11.005),"LaCroix 2019, gnomad v3.1.2, 30554721",Repeat is within a sequencing missing from hg38,,1,615777,,"<1 / 1,000,000 births (orphanet); ½ of DBQD variants (GeneReview). <50 DBQD cases",XYLT1,XYLT1,NBK535148,2019 +chr3,183712188,183712222,183429976,183430010,186521657,186521706,(ATTTT)10.0,FAME4_YEATS2,FAME4,+,TTTTA,TTTCA,ATTTC,,,"TTTTT,TGTTA","TTTTT,ATGTT",Familial adult myoclonic epilepsy 4,YEATS2,,(TTTTA)*(TTTCA)*,AD,Intronic,,0,0,0,,,,>1000,1000,1000,10.0,5,Typical: 20-25 (PMID: 22713812); Range: 10-33 (PMID: 31539032),10,33,20,25,novel,RNA toxicity,RNA toxicity hypothesized,(10.1093/brain/awz267),Pathogenic Short Tandem Repeats Gnomad v3.1.2,,,34,615127,,"FAME overall is 1/35,000 in Japan",YEATS2,YEATS2,NBK535148,2019 +chrX,137566826,137566856,136648985,136649015,135876774,135876800,(CGC)9.0,VACTERLX_ZIC3,VACTERLX,+,GCN,GCN,CNG,,,,,X-linked VACTERL syndrome,ZIC3,,(GCN)*,XR,Coding,,<10,9,10,11,11,11,>12,12,12,9.0,3,0,0,0,0,0,ref,Polyalanine,Polyalanine,(doi.org/10.1038/nature05977),"Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148",,,30,314390,,1 patient with VACTERL died at birth. 8 patients with X-linked OAVS at 11 motifs; 1 individual in OAVS cohort with 12 repeats. ,ZIC3,ZIC3,NBK535148, +chr7,55887601,55887639,55955294,55955332,56047901,56047939,(GCG)15.0,FRA7A_ZNF713,FRA7A,+,GCG,GCG,CGG,,,,,Autism spectrum disorder associated with fragile site FRA7A,ZNF713,,(GCG)*,AD,Intronic,,5-22,5,22,85,85,85,450,450,450,13.0,3,2-3 (four individuals; PMID: 25196122),2,3,2,3,ref,Methylation,Methylation,(OMIM),"OMIM, https://pubmed.ncbi.nlm.nih.gov/25196122/",,,38,616181,,4 individuals,,,, +chr21,43776443,43776479,45196324,45196360,42132055,42132091,,EPM1_CSTB,EPM1,-,CGCGGGGCGGGG,CGCGGGGCGGGG,CCCCGCCCCGCG,,,,,Progressive Myoclonic Epilepsy Type 1 (EPM1) Unverricht-Lundborg Disease (ULD),CSTB,,(CGCGGGGCGGGG)*,AR,Promoter,,2-3,2,3,12-17,12,17,>=30,30,81,,12,Typical: 6-15 (GeneReview); Range: 6-16 (PMID: 9012407),6,16,6,15,,,,,"OMIM, https://www.ncbi.nlm.nih.gov/books/NBK1142/, PMID: 9126745",,,,254800,,"Worldwide prevalence unknown; Finland prevalence 2-4/100,000",,CSTB,NBK1142,1997 +chr17,80147059,80147139,78120858,78120938,81047454,81047534,,RCPS_EIF4A3,RCPS,-,CCTCGCTGTGCCGCTGCCGA,CCTCGCTGTGCCGCTGCCGA,ACAGCGAGGTCGGCAGCGGC,,,,,Richieri-Costa-Pereira syndrome,EIF4A3,,(CCTCGCTGCGCCGCTGCCGA)*(CCTCGCTGTGCCGCTGCCGA)*,AR,5'UTR,,1-9,1,9,10-13,10,13,>14,14,16,,20,0 (birth),0,0,0,0,,,,,https://www.ncbi.nlm.nih.gov/books/NBK535148/,,Complex repeat (GeneReview).,,268305,,49 cases as of Nov 2023 (doi.org/10.1016/j.omsc.2023.100340),,EIF4A3,NBK535148, +chr20,4699397,4699493,4680043,4680139,4738633,4738705,,CJD_PRNP,CJD,+,GGTGGTGGCTGGGGGCAGCCTCAT,CCTCATGGTGGTGGCTGGGGGCAG,AGCCTCATGGTGGTGGCTGGGGGC,,,,,Creutzfeldt-Jakob disease,PRNP,(CCTCAGGGCGGTGGTGGCTGGGGGCAG)1(CCTCATGGTGGTGGCTGGGGGCAG)n,(CCTCAGGGCGGTGGTGGCTGGGGGCAG)*(CCTCATGGTGGTGGCTGGGGGCAG)*,AD,Coding,Exon 2,<=4,,4,,,,>=5,5,,,24,Typical: 50-60 (GeneReview); Range: 31-63 (PMID: 37379724),31,63,50,60,,,,,https://www.ncbi.nlm.nih.gov/books/NBK1229/,,,,123400,,"<0.0225/1,000,000: <15% of CJ variants are repeat expansions (NBK535148). 15% newly diagnosed prion disease cases are genetic (GeneReview) 1 individual per million per year worldwide (350 cases annually in US) (PMID: 29939637) +",,PRNP,NBK1229, +chr1,1435798,1435818,1371178,1371198,870158,870178,,HMNR7_VWA1,HMNR7,+,GGCGCGGAGC,GGCGCGGAGC,AGCGGCGCGG,,,,,"Neuronopathy, distal hereditary motor, autosomal recessive 7",VWA1,,(GGCGCGGAGC)*,AR,Coding,Exon 1,2,2,2,,,,Any deviation from 2,1,3,,10,Typical: 1-3 (PMID: 33559681); Range: 0-10 (OMIM),0,10,1,3,,,,,,,Any deviation from 2 motifs is thought to be pathogenic,,619216,,Biallelic variants found in 0.01% of 100 KGP participants; enriched in those with motor disease. 80% of VWA1 pathogenic variants are expansions/contractions (GeneReview),,VWA1,NBK535148, +chr1,94418422,94418444,94883978,94884000,94266545,94266567,,OPDM_ABCD3,OPDM,+,GCC,GCC,CCG,,,,,Oculopharyngodistal myopathy,ABCD3,,(GCC)*,AD,5'UTR,,3-44,3,44,,,,118-694,118,694,7.7,3,Typical: 24-30; Range: 10-50 (doi.org/10.1101/2023.10.09.23296582),10,50,24,30,,,,,https://doi.org/10.1101/2023.10.09.23296582,,,,,,Unknown,,,,2023 +chr13,102161577,102161726,102813927,102814076,101377640,101377789,,SCA27B_FGF14,SCA27B,-,AAG,AAG,CTT,,,,,Spinocerebellar ataxia 27B,FGF14,,(AAG)*,AD,Intronic,Intron 1,8-249,8,249,250-299,250,299,>300,300,637,50.3,3,Typical: 42-70; Range: 21-87 (NBK599589),21,87,42,70,ref,Haploinsufficiency,Reduced transcript 2,PMCID: PMC10042577,"https://www.omim.org/entry/620174, https://www.cell.com/ajhg/fulltext/S0002-9297(22)00506-7, PMCID: PMC10042577, PMID: 37399286","250-300 pathogenic with incomplete penetrance, >300 complete penetrance",Incomplete penetrance.,,620174,,"Intermediate expansions 1-2% of population, but non-GAA-pure without relation to ataxia. (GeneReview)",FGF14,,NBK599589,2023 +chr16,72787695,72787758,72821594,72821657,78605503,78605569,(GCC)22.3,SCA4_ZFHX3,SCA4,-,GCC,GCC,CGG,,,,,Spinocerebellar ataxia 4,ZFHX3,,(GCC)*,AD,Coding,Last Exon,16-26 (majority 21),16,26,,,,46-64,46,64,21.3,3,Typical: 37- 56; Range: 15 - 60 (PMID: 38035881 - https://doi.org/10.1101/2023.10.03.23296230) ,15,60,37,56,ref,,,,https://doi.org/10.1101/2023.10.03.23296230,,"Expansion found in affected individuals from 3 families and not in any of the 1001 controls. Possible anticipation (PMID: 38197134, PMID: 38035881)",,600223,,Unknown,,,,2023 +chr16,67842863,67842950,67876766,67876853,73638637,73638724,,SCA_THAP11,SCA,+,CAG,CAG,AGC,,,,,Spinocerebellar ataxia,THAP11,,(CAG)*,AD,Coding,Exon 1,20-38,20,38,,,,45-100,45,100,29.3,3,Typical: 8-40; Range: 4-51 (PMID: 37148549),4,51,8,40,ref,PolyQ toxicity,,https://doi.org/10.1002/mds.29412,"https://doi.org/10.1002/mds.29412, https://doi.org/10.1042/ETLS20230018",,"Expansion found in affected individuals from 2 families and not in 500 controls. Longer alleles were associated wither earlier age of onset. For example, an individual with 100 repeats had age of onset at 4 years.",,,,Unknown,,,,2023 diff --git a/data/STR-disease-loci.processed.json b/data/STR-disease-loci.processed.json index ad5e799..af1f20c 100644 --- a/data/STR-disease-loci.processed.json +++ b/data/STR-disease-loci.processed.json @@ -36,9 +36,11 @@ "pathogenic_max": "694", "ref_copies": "7.7", "repeatunitlen": "3", - "age_onset": "average age of onset was 26.7 years (range: 10-50 years)", + "age_onset": "Typical: 24-30; Range: 10-50 (doi.org/10.1101/2023.10.09.23296582)", "age_onset_min": "10", "age_onset_max": "50", + "typ_age_onset_min": "24", + "typ_age_onset_max": "30", "novel": "", "Mechanism": "", "Mechanism_detail": "", @@ -48,8 +50,8 @@ "details": "", "width": "", "OMIM": "", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "Unknown", "STRipy_gene": "", "gnomAD_gene": "", "GeneReviews": "", @@ -92,9 +94,11 @@ "pathogenic_max": "2000", "ref_copies": "50.3", "repeatunitlen": "3", - "age_onset": "2-10", - "age_onset_min": "2", + "age_onset": "Typical: 2-10; Range: 1-10 (developmental delays without physical features can make onset difficult to detect until schooling)", + "age_onset_min": "1", "age_onset_max": "10", + "typ_age_onset_min": "2", + "typ_age_onset_max": "10", "novel": "ref", "Mechanism": "LOF, reduced gene expression", "Mechanism_detail": "Loss of function via transcriptional silencing", @@ -104,8 +108,8 @@ "details": "", "width": "148", "OMIM": "309548", - "Incidence": "", - "Prevalence": "Unknown", + "Prevalence": "2/50000", + "Prevalence_details": "1-4/100,000 males (https://medlineplus.gov/genetics/condition/fragile-xe-syndrome); 1/50-100,000 males, more than 50 families (PMID: 11246464)", "STRipy_gene": "AFF2", "gnomAD_gene": "AFF2", "GeneReviews": "NBK535148", @@ -148,9 +152,11 @@ "pathogenic_max": "300", "ref_copies": "8.7", "repeatunitlen": "3", - "age_onset": "Early childhood", - "age_onset_min": "", - "age_onset_max": "", + "age_onset": "Early childhood (small sample size) (PMID: 24763282)", + "age_onset_min": "1", + "age_onset_max": "7", + "typ_age_onset_min": "", + "typ_age_onset_max": "", "novel": "ref", "Mechanism": "Decreased gene expression, methylation", "Mechanism_detail": "\"silencing of the FMR2 gene as a consequence of a CCG expansion located upstream of this gene\"", @@ -160,8 +166,8 @@ "details": "", "width": "25", "OMIM": "601464", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "1/862 (1/654-1266) population prevalence of methylated AFF3 expansions (mild cognitive disability)\nhttps://www.medrxiv.org/content/10.1101/2023.05.03.23289461v1.full.pdf\n", "STRipy_gene": "", "gnomAD_gene": "", "GeneReviews": "", @@ -204,9 +210,11 @@ "pathogenic_max": "68", "ref_copies": "34.0", "repeatunitlen": "3", - "age_onset": "20-49", - "age_onset_min": "20", - "age_onset_max": "49", + "age_onset": "Typical: 20-49 (OMIM), Range: 15-75 (https://doi.org/10.1038/sj.ejhg.5200656) ", + "age_onset_min": "15", + "age_onset_max": "75", + "typ_age_onset_min": "20", + "typ_age_onset_max": "49", "novel": "ref", "Mechanism": "Polyglutamine", "Mechanism_detail": "Polyglutamine", @@ -216,8 +224,8 @@ "details": "", "width": "102", "OMIM": "313200", - "Incidence": "", - "Prevalence": "1:300,000 males (SBMA); 1/40,000 (Kennedy Disease)", + "Prevalence": "1/30000", + "Prevalence_details": "1-2/100,000 (population-specific, higher in Finnish population, Canadian population) (PMID: 37628685); 1/30,000 (Orphanet) ; mutation frequency of 1:3182 10x more frequent than reported disease prevalence of 1 in 30,000 (PMID: 36797998); Tang et al., 2017: 0.67-2.5/100,000", "STRipy_gene": "AR", "gnomAD_gene": "AR", "GeneReviews": "NBK1333", @@ -260,9 +268,11 @@ "pathogenic_max": "27", "ref_copies": "14.7", "repeatunitlen": "3", - "age_onset": "0", + "age_onset": "Typical: 0 (PMID: 21204215, PMID: 9307258, OMIM); Range: 0-4 (Childhood epilepsy, cognitive disability, \u223c70% of cases infantile spasms --> seizures by 3 or 4 years re: PMID: 19587282)", "age_onset_min": "0", - "age_onset_max": "0", + "age_onset_max": "4", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine", "Mechanism_detail": "Polyalanine", @@ -272,8 +282,8 @@ "details": "", "width": "43", "OMIM": "308350; 300419; 300215", - "Incidence": "1-2/100,000", - "Prevalence": "~<1/35,000", + "Prevalence": "", + "Prevalence_details": "Unknown", "STRipy_gene": "ARX_1", "gnomAD_gene": "ARX_1", "GeneReviews": "NBK535148", @@ -316,9 +326,11 @@ "pathogenic_max": "20", "ref_copies": "12.0", "repeatunitlen": "3", - "age_onset": "1-3", - "age_onset_min": "1", - "age_onset_max": "3", + "age_onset": "Typical: 1-3; Range: 0-4 (OMIM); Mildness can make diagnosis difficult (particularly mild/absent in females) ", + "age_onset_min": "0", + "age_onset_max": "4", + "typ_age_onset_min": "1", + "typ_age_onset_max": "3", "novel": "ref", "Mechanism": "Polyalanine", "Mechanism_detail": "Polyalanine", @@ -328,8 +340,8 @@ "details": "", "width": "35", "OMIM": "309510", - "Incidence": "", - "Prevalence": "Unknown", + "Prevalence": "", + "Prevalence_details": "Unknown", "STRipy_gene": "ARX_2", "gnomAD_gene": "ARX_2", "GeneReviews": "NBK535148", @@ -372,9 +384,11 @@ "pathogenic_max": "93", "ref_copies": "19.0", "repeatunitlen": "3", - "age_onset": "1-72", - "age_onset_min": "1", + "age_onset": "Typical: 20-40 (PMID: 6808417, NBK1491)\nRange: 0 (PMID: 11160976) - 72 (NBK1491)", + "age_onset_min": "0", "age_onset_max": "72", + "typ_age_onset_min": "20", + "typ_age_onset_max": "40", "novel": "ref", "Mechanism": "Polyglutamine", "Mechanism_detail": "Polyglutamine", @@ -384,8 +398,8 @@ "details": "", "width": "58", "OMIM": "125370", - "Incidence": "", - "Prevalence": "2-7/1,000,000", + "Prevalence": "4.5/1000000", + "Prevalence_details": "2-7/1,000,000", "STRipy_gene": "ATN1", "gnomAD_gene": "ATN1", "GeneReviews": "NBK1491", @@ -428,9 +442,11 @@ "pathogenic_max": "91", "ref_copies": "30.3", "repeatunitlen": "3", - "age_onset": "20-40 typical", - "age_onset_min": "13", - "age_onset_max": "60", + "age_onset": "Typical: 20-39 (UptoDate); Range: 6(PMID: 3165612)-63 (PMID: 8825276)", + "age_onset_min": "6", + "age_onset_max": "63", + "typ_age_onset_min": "20", + "typ_age_onset_max": "39", "novel": "ref", "Mechanism": "Polyglutamine", "Mechanism_detail": "Polyglutamine", @@ -440,8 +456,8 @@ "details": "", "width": "90", "OMIM": "164400", - "Incidence": "", - "Prevalence": "1-2/100,000", + "Prevalence": "1.5/100000", + "Prevalence_details": "1-2/100,000", "STRipy_gene": "ATXN1", "gnomAD_gene": "ATXN1", "GeneReviews": "NBK1184", @@ -484,9 +500,11 @@ "pathogenic_max": "4500", "ref_copies": "14.0", "repeatunitlen": "5", - "age_onset": "12-48", - "age_onset_min": "12", - "age_onset_max": "48", + "age_onset": "Typical: 12-48; Range: 11-83 (NBK1175)", + "age_onset_min": "11", + "age_onset_max": "83", + "typ_age_onset_min": "12", + "typ_age_onset_max": "48", "novel": "ref", "Mechanism": "Unknown", "Mechanism_detail": "Transdominant mechanism theorized", @@ -496,8 +514,8 @@ "details": "", "width": "69", "OMIM": "603516", - "Incidence": "", - "Prevalence": "Unknown", + "Prevalence": "", + "Prevalence_details": "Unknown; >300 individuals (GeneReview)", "STRipy_gene": "ATXN10", "gnomAD_gene": "ATXN10", "GeneReviews": "", @@ -540,9 +558,11 @@ "pathogenic_max": "200", "ref_copies": "23.3", "repeatunitlen": "3", - "age_onset": "30-40 typical", - "age_onset_min": "25", - "age_onset_max": "50", + "age_onset": "Typical: 30-39 (GeneReview); Range: 2-86 (OMIM)", + "age_onset_min": "2", + "age_onset_max": "86", + "typ_age_onset_min": "30", + "typ_age_onset_max": "39", "novel": "ref", "Mechanism": "Polyglutamine ", "Mechanism_detail": "Polyglutamine ", @@ -552,8 +572,8 @@ "details": "", "width": "69", "OMIM": "183090", - "Incidence": "", - "Prevalence": "1-2/100,000 (population dependent)", + "Prevalence": "1.5/100000", + "Prevalence_details": "1-2/100,000 (Tang et al., 2017) (population dependent)", "STRipy_gene": "ATXN2", "gnomAD_gene": "ATXN2", "GeneReviews": "NBK1275", @@ -596,9 +616,11 @@ "pathogenic_max": "87", "ref_copies": "14.0", "repeatunitlen": "3", - "age_onset": "10-50 typical", - "age_onset_min": "10", - "age_onset_max": "50", + "age_onset": "Typical: 10-49 (GeneReview); 5-73 (GeneReview; PMID: 30414314)", + "age_onset_min": "5", + "age_onset_max": "73", + "typ_age_onset_min": "10", + "typ_age_onset_max": "49", "novel": "ref", "Mechanism": "Polyglutamine ", "Mechanism_detail": "Polyglutamine ", @@ -608,8 +630,8 @@ "details": "", "width": "41", "OMIM": "109150", - "Incidence": "", - "Prevalence": "1\u20135/100,000", + "Prevalence": "2.1/100000", + "Prevalence_details": "1\u20135/100,000, Tang et al., 2017; Most prevalence SCA subtype (NBK557816)", "STRipy_gene": "ATXN3", "gnomAD_gene": "ATXN3", "GeneReviews": "NBK1196", @@ -652,9 +674,11 @@ "pathogenic_max": "460", "ref_copies": "10.7", "repeatunitlen": "3", - "age_onset": "0-50", + "age_onset": "Typical: 4-48 (PMID: 20739808); Range: 0-65 (GeneReview)", "age_onset_min": "0", - "age_onset_max": "50", + "age_onset_max": "65", + "typ_age_onset_min": "4", + "typ_age_onset_max": "48", "novel": "ref", "Mechanism": "Polyglutamine ", "Mechanism_detail": "Polyglutamine ", @@ -664,8 +688,8 @@ "details": "", "width": "31", "OMIM": "164500", - "Incidence": "", - "Prevalence": "<1/300,000", + "Prevalence": ".999/300000", + "Prevalence_details": "<1/300,000 (GeneReview)", "STRipy_gene": "ATXN7", "gnomAD_gene": "ATXN7", "GeneReviews": "NBK1256", @@ -708,9 +732,11 @@ "pathogenic_max": "1300", "ref_copies": "15.3", "repeatunitlen": "3", - "age_onset": "20-50 typical", + "age_onset": "Typical: 20-40; Range: 0-73 (GeneReview)", "age_onset_min": "1", "age_onset_max": "73", + "typ_age_onset_min": "20", + "typ_age_onset_max": "49", "novel": "ref", "Mechanism": "Polyglutamine/toxic gain-of-function; Unknown ", "Mechanism_detail": "Polyglutamine/toxic gain-of-function; Unknown ", @@ -720,8 +746,8 @@ "details": "", "width": "46", "OMIM": "608768", - "Incidence": "", - "Prevalence": "<1/100,000", + "Prevalence": "0.5/100000", + "Prevalence_details": "<1/100,000; Tang et al., 2017; Expansion in 1:100-1200 chromosomes (GeneReview)", "STRipy_gene": "ATXN8OS", "gnomAD_gene": "ATXN8OS", "GeneReviews": "NBK1268", @@ -764,9 +790,11 @@ "pathogenic_max": "760", "ref_copies": "14.4", "repeatunitlen": "5", - "age_onset": "20-72", - "age_onset_min": "20", - "age_onset_max": "72", + "age_onset": "Typical: 56-62 (PMID: 36563608); Range: 8-83 (PMID: 23331413) ", + "age_onset_min": "8", + "age_onset_max": "83", + "typ_age_onset_min": "56", + "typ_age_onset_max": "62", "novel": "novel", "Mechanism": "Epigenetic", "Mechanism_detail": "Role in heterochromatin or chromosomal structure theorized ", @@ -776,8 +804,8 @@ "details": "", "width": "69", "OMIM": "117210", - "Incidence": "", - "Prevalence": "Unknown (more common in Japanese pop)", + "Prevalence": "", + "Prevalence_details": "Unknown (more common in Japanese pop)", "STRipy_gene": "BEAN1", "gnomAD_gene": "BEAN1", "GeneReviews": "NBK535148", @@ -820,9 +848,11 @@ "pathogenic_max": "2000", "ref_copies": "10.8", "repeatunitlen": "6", - "age_onset": "27-85", - "age_onset_min": "27", - "age_onset_max": "85", + "age_onset": "Typical: 50-64; Range: 20-91 (GeneReview)", + "age_onset_min": "20", + "age_onset_max": "91", + "typ_age_onset_min": "50", + "typ_age_onset_max": "64", "novel": "ref", "Mechanism": "RNA toxicity proposed", "Mechanism_detail": "\"The HRE forms DNA and RNA G-quadruplexes with distinct structures and promotes RNA/DNA hybrids (R-loops). The structural polymorphism causes a repeat length-dependent accumulation of transcripts aborted in the HRE region.\"", @@ -832,8 +862,8 @@ "details": "", "width": "62", "OMIM": "105500", - "Incidence": "", - "Prevalence": "The expansion of a hexanucleotide repeat GGGGCC in C9orf72 is the most common known cause of ALS accounting for ~ 40% familial cases and ~ 7% sporadic cases in the European population", + "Prevalence": "", + "Prevalence_details": "The expansion of a hexanucleotide repeat GGGGCC in C9orf72 is the most common known cause of ALS accounting for ~ 40% familial cases and ~ 7% sporadic cases in the European population; overall ALS incidence is 1-2/100,000 person-years, point prevalence is 3-5/100,000 (Europe/US); lifetime risk is 1 in 300 (PMID: 31315673). C9orf72-FTD is estimated to be 0.04-134:100,000 (GeneReview), and by our estimates 0.65-1.56/100,000 for C9orf72-ALS. ", "STRipy_gene": "C9ORF72", "gnomAD_gene": "C9ORF72", "GeneReviews": "NBK268647", @@ -876,9 +906,11 @@ "pathogenic_max": "33", "ref_copies": "13.3", "repeatunitlen": "3", - "age_onset": "19-73", - "age_onset_min": "19", + "age_onset": "Typical: 43-52 (GeneReview); Range: 16 (PMID: 23331413) - 73 (NBK1140)", + "age_onset_min": "16", "age_onset_max": "73", + "typ_age_onset_min": "43", + "typ_age_onset_max": "52", "novel": "ref", "Mechanism": "Polyglutamine ", "Mechanism_detail": "Polyglutamine ", @@ -888,8 +920,8 @@ "details": "", "width": "39", "OMIM": "183086", - "Incidence": "", - "Prevalence": "<1/1,000,000", + "Prevalence": "0.3/100000", + "Prevalence_details": "13-15% of global SCA prevalence, estimated to be 0.02-31/100,000 (GeneReview); Tang et al., 2017: 0.3-5/100,000", "STRipy_gene": "CACNA1A", "gnomAD_gene": "CACNA1A", "GeneReviews": "NBK1140", @@ -932,9 +964,11 @@ "pathogenic_max": "100", "ref_copies": "11.3", "repeatunitlen": "3", - "age_onset": "", + "age_onset": "Condition at birth.", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "", + "typ_age_onset_max": "", "novel": "ref", "Mechanism": "", "Mechanism_detail": "No information found", @@ -944,8 +978,8 @@ "details": "", "width": "33", "OMIM": "147791", - "Incidence": "", - "Prevalence": "1/100,000 births", + "Prevalence": "", + "Prevalence_details": "1/100,000 births; female/male ratio 2:1 (PMID: 19267933); expansion can lead to deletion (shown in 2 cases) but total causality is unclear", "STRipy_gene": "CBL", "gnomAD_gene": "", "GeneReviews": "", @@ -988,20 +1022,22 @@ "pathogenic_max": "11000", "ref_copies": "20.8", "repeatunitlen": "4", - "age_onset": "~30-40", - "age_onset_min": "30", - "age_onset_max": "40", + "age_onset": "Typical: 28-56 (PMID: 29086017); Range: 0-73 (PMID: 31159885)", + "age_onset_min": "0", + "age_onset_max": "73", + "typ_age_onset_min": "28", + "typ_age_onset_max": "56", "novel": "ref", "Mechanism": "Aberrant splicing", "Mechanism_detail": "Aberrant splicing", "Mechanism_source": "(doi.org/10.1093/hmg/ddr568)", "source": "Hannan 2018, Mirkin 2007, GeneReviews NBK1466, https://doi.org/10.1038/s41580-021-00382-6", "notes": "(TG)n(TCTG)n(CCTG)n. CCTG expansion causes DM2 but the other repeat units are also variable.", - "details": "", + "details": "Penetrance is age-dependent and approaches 100%", "width": "82", "OMIM": "602668", - "Incidence": "", - "Prevalence": "2.29/100,000", + "Prevalence": "2.29/100000", + "Prevalence_details": "2.29/100,000 (PMID: 35483324); population specific prevalence (GeneReview)", "STRipy_gene": "CNBP", "gnomAD_gene": "CNBP", "GeneReviews": "NBK1466", @@ -1044,9 +1080,11 @@ "pathogenic_max": "7", "ref_copies": "5.0", "repeatunitlen": "3", - "age_onset": "13", - "age_onset_min": "13", + "age_onset": "Typical: 0-2 (COMP-PSACH)/ 1-12 (EDM1); Range: 0 (PSACH) - 13 (EDM1)", + "age_onset_min": "0", "age_onset_max": "13", + "typ_age_onset_min": "0", + "typ_age_onset_max": "12", "novel": "ref", "Mechanism": "Protein LOF", "Mechanism_detail": "LOF, domain dependent", @@ -1056,8 +1094,8 @@ "details": "", "width": "15", "OMIM": "132400; 177170", - "Incidence": "", - "Prevalence": "9-16/100,000 births", + "Prevalence": "", + "Prevalence_details": "Specific contribution of COMP repeats to EDM1 is unknown (~300 COMP mutation variants for both phenotypes); likely 1:90,000 prevalence for COMP-PSACH that is repeat-specific.", "STRipy_gene": "COMP", "gnomAD_gene": "COMP", "GeneReviews": "NBK1123; NBK1487", @@ -1100,9 +1138,11 @@ "pathogenic_max": "81", "ref_copies": "", "repeatunitlen": "12", - "age_onset": "6-15", + "age_onset": "Typical: 6-15 (GeneReview); Range: 6-16 (PMID: 9012407)", "age_onset_min": "6", - "age_onset_max": "15", + "age_onset_max": "16", + "typ_age_onset_min": "6", + "typ_age_onset_max": "15", "novel": "", "Mechanism": "", "Mechanism_detail": "", @@ -1112,8 +1152,8 @@ "details": "", "width": "", "OMIM": "254800", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "Worldwide prevalence unknown; Finland prevalence 2-4/100,000", "STRipy_gene": "", "gnomAD_gene": "CSTB", "GeneReviews": "NBK1142", @@ -1156,9 +1196,11 @@ "pathogenic_max": "75", "ref_copies": "16.6", "repeatunitlen": "5", - "age_onset": "18-64", + "age_onset": "Typical: 33-53; Range: 18-64 (GeneReview)", "age_onset_min": "18", "age_onset_max": "64", + "typ_age_onset_min": "33", + "typ_age_onset_max": "53", "novel": "novel", "Mechanism": "Protein toxic GOF", "Mechanism_detail": "toxic gain-of-function mechanism", @@ -1168,8 +1210,8 @@ "details": "", "width": "81", "OMIM": "615945", - "Incidence": "", - "Prevalence": "<1/1,000,000", + "Prevalence": "", + "Prevalence_details": "0.20/100,000 specific to Portugal; not yet found in other geographic regions", "STRipy_gene": "DAB1", "gnomAD_gene": "DAB1", "GeneReviews": "NBK541729", @@ -1212,9 +1254,11 @@ "pathogenic_max": "306", "ref_copies": "7.0", "repeatunitlen": "3", - "age_onset": "", - "age_onset_min": "1", - "age_onset_max": "1", + "age_onset": "Typical: 0-1 (PMID: 3742859); Range: 0-3 (PMID: 4042396)", + "age_onset_min": "0", + "age_onset_max": "3", + "typ_age_onset_min": "0", + "typ_age_onset_max": "1", "novel": "ref", "Mechanism": "Increased gene expression, methylation", "Mechanism_detail": "Increased gene expression, methylation", @@ -1224,8 +1268,8 @@ "details": "", "width": "20", "OMIM": "136630", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "", "STRipy_gene": "DIP2B", "gnomAD_gene": "DIP2B", "GeneReviews": "NBK535148", @@ -1268,9 +1312,11 @@ "pathogenic_max": "82", "ref_copies": "16.7", "repeatunitlen": "3", - "age_onset": "dependent on repeat number (birth to adulthood)", - "age_onset_min": "0", - "age_onset_max": "3", + "age_onset": "Typical: 6-7 (usual disease is 0-3)", + "age_onset_min": "6", + "age_onset_max": "7", + "typ_age_onset_min": "6", + "typ_age_onset_max": "7", "novel": "ref", "Mechanism": "Protein LOF", "Mechanism_detail": "Functional defect in dystrophin/dystroglycan", @@ -1280,8 +1326,8 @@ "details": "There is conflicting evidence for the association between this repeat expansion and Duchenne muscular dystrophy. The association was reported in a single family (PMID: 27417533). The population frequency of the proposed pathogenic allele is much higher than expected for a highly penetrant early-onset condition.", "width": "48", "OMIM": "310200", - "Incidence": "", - "Prevalence": "", + "Prevalence": "4.8/100000", + "Prevalence_details": "Believed to be 0 for disease specific to STR expansion. 1/3500-4700 male births (incidence) for overall DMD (one of the most common and severe congenital myopathies). 4.8/100,000 prevalence PMID: 35168641", "STRipy_gene": "DMD", "gnomAD_gene": "DMD", "GeneReviews": "NBK535148", @@ -1324,9 +1370,11 @@ "pathogenic_max": "1000", "ref_copies": "20.7", "repeatunitlen": "3", - "age_onset": "0-30, mild up to 70", + "age_onset": "Typical: 10-30 (\"classic\", GeneReview); Range: 0-74 (PMID: 38454488)", "age_onset_min": "0", - "age_onset_max": "70", + "age_onset_max": "74", + "typ_age_onset_min": "10", + "typ_age_onset_max": "30", "novel": "ref", "Mechanism": "RNA GOF", "Mechanism_detail": "RNA gain-of-function - RNA gelation leading to misregulation of alternative splicing", @@ -1336,8 +1384,8 @@ "details": "", "width": "62", "OMIM": "160900", - "Incidence": "", - "Prevalence": "5-20/100,000", + "Prevalence": "8/100000", + "Prevalence_details": "5-20/100,000 (GeneReview); Tang et al., 2017: 0.5-18.1/100,000; 6.5/100,000 (PMID: 31159885) ; 9.27 cases (95% CI: 4.73-15.21) per 100,000, ranging from 0.37 to 36.29 cases per 100,000 (PMID: 35483324)", "STRipy_gene": "DMPK", "gnomAD_gene": "DMPK", "GeneReviews": "NBK1165", @@ -1380,20 +1428,22 @@ "pathogenic_max": "16", "ref_copies": "", "repeatunitlen": "20", - "age_onset": "0", + "age_onset": "0 (birth)", "age_onset_min": "0", - "age_onset_max": "", + "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "", "Mechanism": "", "Mechanism_detail": "", "Mechanism_source": "", "source": "https://www.ncbi.nlm.nih.gov/books/NBK535148/", "notes": "", - "details": "", + "details": "Complex repeat (GeneReview).", "width": "", "OMIM": "268305", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "49 cases as of Nov 2023 (doi.org/10.1016/j.omsc.2023.100340)", "STRipy_gene": "", "gnomAD_gene": "EIF4A3", "GeneReviews": "NBK535148", @@ -1436,23 +1486,25 @@ "pathogenic_max": "637", "ref_copies": "50.3", "repeatunitlen": "3", - "age_onset": "mean 55\u00b113 for episodic symptoms, 59\u00b111 for progressive ataxia", - "age_onset_min": "30", - "age_onset_max": "88", + "age_onset": "Typical: 42-70; Range: 21-87 (NBK599589)", + "age_onset_min": "21", + "age_onset_max": "87", + "typ_age_onset_min": "42", + "typ_age_onset_max": "70", "novel": "ref", "Mechanism": "Haploinsufficiency", "Mechanism_detail": "Reduced transcript 2", "Mechanism_source": "PMCID: PMC10042577", "source": "https://www.omim.org/entry/620174, https://www.cell.com/ajhg/fulltext/S0002-9297(22)00506-7, PMCID: PMC10042577, PMID: 37399286", "notes": "250-300 pathogenic with incomplete penetrance, >300 complete penetrance", - "details": "", + "details": "Incomplete penetrance.", "width": "", "OMIM": "620174", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "Intermediate expansions 1-2% of population, but non-GAA-pure without relation to ataxia. (GeneReview)", "STRipy_gene": "FGF14", "gnomAD_gene": "", - "GeneReviews": "", + "GeneReviews": "NBK599589", "Year": "2023" }, { @@ -1492,9 +1544,11 @@ "pathogenic_max": "2000", "ref_copies": "20.6667", "repeatunitlen": "3", - "age_onset": "FXS 2, FXTAS 60-65", - "age_onset_min": "2", - "age_onset_max": "65", + "age_onset": "Typical: FXS 1 to \"first several yeares of life\", FXTAS 60-65 (GeneReview); Range: 0 (FXS, UptoDate) - 78 (PMID: 17427188)", + "age_onset_min": "0", + "age_onset_max": "78", + "typ_age_onset_min": "1", + "typ_age_onset_max": "65", "novel": "ref", "Mechanism": "LOF via decreased gene expression in FXS, GOF in FXTAS", "Mechanism_detail": "Loss of function via transcriptional silencing in FXSRNA GOF in FXTAS", @@ -1504,8 +1558,8 @@ "details": "", "width": "74", "OMIM": "300624; 300623", - "Incidence": "", - "Prevalence": "16-25/100,000 males", + "Prevalence": "19/100000", + "Prevalence_details": "16-25/100,000 males; Tang et al., 2017: known carrier frequency 300-500/100,000 but detected was 11/100,000", "STRipy_gene": "FMR1", "gnomAD_gene": "FMR1", "GeneReviews": "NBK1384", @@ -1548,9 +1602,11 @@ "pathogenic_max": "15", "ref_copies": "14.0", "repeatunitlen": "3", - "age_onset": "0, can have infertility in childbearing age", + "age_onset": "0 (birth)", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine", "Mechanism_detail": "Polyalanine", @@ -1560,8 +1616,8 @@ "details": "", "width": "42", "OMIM": "110100", - "Incidence": "", - "Prevalence": "1 in 50,000 births globally", + "Prevalence": "0.31/50000", + "Prevalence_details": "1 in 50,000 births globally for all BPES, with FOXL2 expansions 31% of pathogenic variants (NBK1441; NBK535148)", "STRipy_gene": "FOXL2", "gnomAD_gene": "FOXL2", "GeneReviews": "NBK535148", @@ -1604,9 +1660,11 @@ "pathogenic_max": "1700", "ref_copies": "6.0", "repeatunitlen": "3", - "age_onset": "5-25", - "age_onset_min": "5", - "age_onset_max": "25", + "age_onset": "Typical: 10-15; Range: 2-80 (GeneReview)", + "age_onset_min": "2", + "age_onset_max": "80", + "typ_age_onset_min": "10", + "typ_age_onset_max": "15", "novel": "ref", "Mechanism": "LOF, reduced gene expression", "Mechanism_detail": "Loss of function via transcriptional silencing", @@ -1616,8 +1674,8 @@ "details": "", "width": "2", "OMIM": "229300", - "Incidence": "", - "Prevalence": "1/50,000 (US), 1/40,000 (global)", + "Prevalence": "1/50000", + "Prevalence_details": "1/50,000 (OMIM); Tang et al., 2017: Known carrier frequency 1000/100,000; observed 421/100,000", "STRipy_gene": "FXN", "gnomAD_gene": "FXN", "GeneReviews": "NBK1281", @@ -1660,9 +1718,11 @@ "pathogenic_max": "138", "ref_copies": "14.7", "repeatunitlen": "3", - "age_onset": "10-29", - "age_onset_min": "10", - "age_onset_max": "29", + "age_onset": "Typical: 20-34 (PMID: 32413282); Range: 14 (PMID: ...282) - 70 (PMID: 33374016)", + "age_onset_min": "14", + "age_onset_max": "70", + "typ_age_onset_min": "20", + "typ_age_onset_max": "34", "novel": "ref", "Mechanism": "RNA toxicity", "Mechanism_detail": "RNA mediated toxicity hypothesized; unknown", @@ -1672,8 +1732,8 @@ "details": "", "width": "33", "OMIM": "618940", - "Incidence": "", - "Prevalence": "Population dependent", + "Prevalence": "", + "Prevalence_details": "Population dependent; presumed rare.", "STRipy_gene": "GIPC1", "gnomAD_gene": "GIPC1", "GeneReviews": "NBK535148", @@ -1716,9 +1776,11 @@ "pathogenic_max": "1500", "ref_copies": "16.0", "repeatunitlen": "3", - "age_onset": "Early childhood", - "age_onset_min": "0", - "age_onset_max": "1", + "age_onset": "Early childhood (2-4; PMID: 30970188, 35913761)", + "age_onset_min": "2", + "age_onset_max": "4", + "typ_age_onset_min": "2", + "typ_age_onset_max": "4", "novel": "ref", "Mechanism": "Decreased gene expression, methylation", "Mechanism_detail": "Change in histone modification decreases transcription", @@ -1728,8 +1790,8 @@ "details": "", "width": "47", "OMIM": "618412", - "Incidence": "", - "Prevalence": "As of 2019, only 7 cases", + "Prevalence": "", + "Prevalence_details": "As of 2019, only 7 cases total of GLS deficiency, including non-repeat", "STRipy_gene": "GLS", "gnomAD_gene": "GLS", "GeneReviews": "NBK535148", @@ -1772,9 +1834,11 @@ "pathogenic_max": "32", "ref_copies": "18.0", "repeatunitlen": "3", - "age_onset": "0", + "age_onset": "0 (birth)", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine ", "Mechanism_detail": "Polyalanine ", @@ -1784,8 +1848,8 @@ "details": "", "width": "54", "OMIM": "140000", - "Incidence": "", - "Prevalence": "Rare", + "Prevalence": "", + "Prevalence_details": "\"Extremely rare\" (GeneReview)", "STRipy_gene": "HOXA13_3", "gnomAD_gene": "HOXA13_3", "GeneReviews": "NBK1423", @@ -1828,9 +1892,11 @@ "pathogenic_max": "18", "ref_copies": "12.0", "repeatunitlen": "3", - "age_onset": "0", + "age_onset": "0 (birth)", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine ", "Mechanism_detail": "Polyalanine ", @@ -1840,8 +1906,8 @@ "details": "", "width": "36", "OMIM": "140000", - "Incidence": "", - "Prevalence": "Rare", + "Prevalence": "", + "Prevalence_details": "\"Extremely rare\" (GeneReview)", "STRipy_gene": "HOXA13_2", "gnomAD_gene": "HOXA13_2", "GeneReviews": "NBK1423", @@ -1884,9 +1950,11 @@ "pathogenic_max": "22", "ref_copies": "14.0", "repeatunitlen": "3", - "age_onset": "0", + "age_onset": "0 (birth)", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine ", "Mechanism_detail": "Polyalanine ", @@ -1896,8 +1964,8 @@ "details": "", "width": "42", "OMIM": "140000", - "Incidence": "", - "Prevalence": "Rare", + "Prevalence": "", + "Prevalence_details": "\"Extremely rare\" (GeneReview)", "STRipy_gene": "HOXA13_1", "gnomAD_gene": "HOXA13_1", "GeneReviews": "NBK1423", @@ -1940,9 +2008,11 @@ "pathogenic_max": "22", "ref_copies": "14.0", "repeatunitlen": "3", - "age_onset": "0", + "age_onset": "0 (birth)", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine", "Mechanism_detail": "Polyalanine", @@ -1952,8 +2022,8 @@ "details": "", "width": "45", "OMIM": "186000", - "Incidence": "", - "Prevalence": "Unknown", + "Prevalence": "", + "Prevalence_details": "3 individuals (GeneReview)", "STRipy_gene": "HOXD13", "gnomAD_gene": "HOXD13", "GeneReviews": "NBK535148", @@ -1996,9 +2066,11 @@ "pathogenic_max": "250", "ref_copies": "21.3", "repeatunitlen": "3", - "age_onset": "35-44", - "age_onset_min": "3", - "age_onset_max": "70", + "age_onset": "Typical: 35-44 (GeneReview); Range: 2-85 (PMID: 21171977)", + "age_onset_min": "2", + "age_onset_max": "85", + "typ_age_onset_min": "35", + "typ_age_onset_max": "44", "novel": "ref", "Mechanism": "Polyglutamine ", "Mechanism_detail": "Polyglutamine ", @@ -2008,8 +2080,8 @@ "details": "", "width": "63", "OMIM": "143100", - "Incidence": "", - "Prevalence": "1/10,000", + "Prevalence": "1/10000", + "Prevalence_details": "Tang et al., 2017: 6.5-15/100,000; 9.71-17:100,000 (European) vs. 0.1-2/100,000 (African), as many as 1 in 400 have reduced penetrance (0.2-2% for 36-38 CAG) HTT alleles (GeneReview)", "STRipy_gene": "HTT", "gnomAD_gene": "HTT", "GeneReviews": "NBK1305", @@ -2052,9 +2124,11 @@ "pathogenic_max": "58", "ref_copies": "15.6667", "repeatunitlen": "3", - "age_onset": "12-66", + "age_onset": "Typical: 30-52; Range: 12-66 (GeneReview)", "age_onset_min": "12", "age_onset_max": "66", + "typ_age_onset_min": "30", + "typ_age_onset_max": "52", "novel": "ref", "Mechanism": "", "Mechanism_detail": "\"unstable vertical transmission\"", @@ -2064,8 +2138,8 @@ "details": "", "width": "46", "OMIM": "606438", - "Incidence": "", - "Prevalence": "<1/1,000,000", + "Prevalence": "", + "Prevalence_details": "<1/1,000,000 (Orphanet); largely in individuals of African descent", "STRipy_gene": "JPH3", "gnomAD_gene": "JPH3", "GeneReviews": "NBK1529", @@ -2108,9 +2182,11 @@ "pathogenic_max": "90", "ref_copies": "11.7", "repeatunitlen": "3", - "age_onset": "Adult onset, variable (mean 22.1 in one study)", + "age_onset": "Typical: 31-51 (PMID: 34047774); Range: 7-66 (PMID: 2124290)", "age_onset_min": "7", - "age_onset_max": "50", + "age_onset_max": "66", + "typ_age_onset_min": "31", + "typ_age_onset_max": "51", "novel": "ref", "Mechanism": "RNA toxicity", "Mechanism_detail": "RNA mediated toxicity hypothesized; unknown", @@ -2120,8 +2196,8 @@ "details": "", "width": "27", "OMIM": "164310", - "Incidence": "", - "Prevalence": "Population dependent", + "Prevalence": "", + "Prevalence_details": "Population dependent; unknown percentage of LRP12 pathogenic variants.", "STRipy_gene": "LRP12", "gnomAD_gene": "LRP12", "GeneReviews": "NBK535148", @@ -2164,9 +2240,11 @@ "pathogenic_max": "1035", "ref_copies": "14.8", "repeatunitlen": "5", - "age_onset": "10-40", + "age_onset": "Typical: 24-41 (PMID: 19616813); Range: 10 (OMIM) - 46 (PMID: 31664039)", "age_onset_min": "10", - "age_onset_max": "40", + "age_onset_max": "46", + "typ_age_onset_min": "24", + "typ_age_onset_max": "41", "novel": "novel", "Mechanism": "Unknown", "Mechanism_detail": "Noted as unknown in literature", @@ -2176,8 +2254,8 @@ "details": "", "width": "72", "OMIM": "613608", - "Incidence": "", - "Prevalence": "~<1/35,000", + "Prevalence": "", + "Prevalence_details": "Overall FAME prevalence is < 1/35,000; MARCHF6-caused much smaller", "STRipy_gene": "MARCHF6", "gnomAD_gene": "MARCHF6", "GeneReviews": "NBK535148", @@ -2220,9 +2298,11 @@ "pathogenic_max": "56", "ref_copies": "10.7", "repeatunitlen": "3", - "age_onset": "Variable, 19-46 familial", - "age_onset_min": "19", - "age_onset_max": "46", + "age_onset": "Typical: 44-60 (PMID: 26777436); Range: 25 (PMID: 22378146) - 77 (PMID: 26777436)", + "age_onset_min": "25", + "age_onset_max": "77", + "typ_age_onset_min": "44", + "typ_age_onset_max": "60", "novel": "ref", "Mechanism": "", "Mechanism_detail": "No information found", @@ -2232,8 +2312,8 @@ "details": "", "width": "24", "OMIM": "105400", - "Incidence": "1.5-4.7 per 100,000 person-years (All ALS, Europe/NA)", - "Prevalence": "2.7-7.4/100,000 (All ALS, not just this locus)", + "Prevalence": "", + "Prevalence_details": "2.7-7.4/100,000 (All ALS, not just this locus), NIPA1 + C9orf72 is 0.37% of ALS patients; frequency of NIPA1 expansion in controls is 3.74% (PMID: 31286297)", "STRipy_gene": "NIPA1", "gnomAD_gene": "NIPA1", "GeneReviews": "", @@ -2276,9 +2356,11 @@ "pathogenic_max": "2500", "ref_copies": "7.2", "repeatunitlen": "6", - "age_onset": "~52 (mean)", - "age_onset_min": "48", - "age_onset_max": "57", + "age_onset": "Typical: 40-60 (GeneReview); Range: 28 (PMID: 37810464) - 67 (PMID: 37332636)", + "age_onset_min": "28", + "age_onset_max": "67", + "typ_age_onset_min": "40", + "typ_age_onset_max": "60", "novel": "ref", "Mechanism": "Protein toxic GOF", "Mechanism_detail": "toxic gain-of-function mechanism", @@ -2288,8 +2370,8 @@ "details": "", "width": "42", "OMIM": "614153", - "Incidence": "", - "Prevalence": "Unknown", + "Prevalence": "", + "Prevalence_details": "Western Japan: 3.6% of all SCA; Costa da Morte region of Spain: 6.3% of all SCA(PMID: 37332636); US: 0.7% of large undiagnosed ataxia cohort (PMID: 28761930)", "STRipy_gene": "NOP56", "gnomAD_gene": "NOP56", "GeneReviews": "", @@ -2332,20 +2414,22 @@ "pathogenic_max": "517", "ref_copies": "13.3", "repeatunitlen": "3", - "age_onset": "16-76", - "age_onset_min": "16", - "age_onset_max": "76", + "age_onset": "Typical: 30-70 (OMIM); Range: 10 (PMID: 37090934) - 78 (PMID: 37305750)", + "age_onset_min": "10", + "age_onset_max": "78", + "typ_age_onset_min": "30", + "typ_age_onset_max": "70", "novel": "ref", "Mechanism": "Unknown", "Mechanism_detail": "May relate to methylation or RNA pathogenicity; Unknown", "Mechanism_source": "(OMIM) (doi.org/10.1007/s11604-022-01343-5)", "source": "doi: 10.1038/s41588-019-0458-z, https://doi.org/10.1016/j.ajhg.2019.05.013, s40478-021-01201-x", "notes": "May be issues with parology between genes: C253572.1, NOTCH2, NOTCH2NL, NBPF14, NBPF19 ?? Motif variation in controls: (AGG)(CGG)n(AGG)0-3(CGG)0-2. Methylation involved", - "details": "", + "details": "Age of onset inversely related to allele size (PMID: 38377026)", "width": "39", "OMIM": "603472", - "Incidence": "", - "Prevalence": "Unknown", + "Prevalence": "", + "Prevalence_details": ">400 patients reported in literature (PMID: 37371433)", "STRipy_gene": "NOTCH2NLC", "gnomAD_gene": "NOTCH2NLC", "GeneReviews": "NBK535148", @@ -2388,9 +2472,11 @@ "pathogenic_max": "700", "ref_copies": "7.0", "repeatunitlen": "3", - "age_onset": "", + "age_onset": "15-40 (PMID: 31332380; only characterized in one family)", "age_onset_min": "15", "age_onset_max": "40", + "typ_age_onset_min": "15", + "typ_age_onset_max": "40", "novel": "ref", "Mechanism": "RNA toxicity", "Mechanism_detail": "RNA mediated toxicity hypothesized, unknown", @@ -2400,8 +2486,8 @@ "details": "", "width": "21", "OMIM": "618637", - "Incidence": "", - "Prevalence": "Couldn't find", + "Prevalence": "", + "Prevalence_details": "\"Rare\"", "STRipy_gene": "NUTM2B-AS1", "gnomAD_gene": "NUTM2B-AS1", "GeneReviews": "NBK535148", @@ -2444,9 +2530,11 @@ "pathogenic_max": "17", "ref_copies": "7.0", "repeatunitlen": "3", - "age_onset": "26-65", - "age_onset_min": "26", - "age_onset_max": "65", + "age_onset": "Typical: 40-59 (PMID: 37519616); Range: 20-79 (PMID: 35112761)", + "age_onset_min": "20", + "age_onset_max": "79", + "typ_age_onset_min": "40", + "typ_age_onset_max": "59", "novel": "ref", "Mechanism": "Polyalanine ", "Mechanism_detail": "Polyalanine ", @@ -2456,8 +2544,8 @@ "details": "", "width": "20", "OMIM": "164300", - "Incidence": "", - "Prevalence": "1/100,000 Western countries", + "Prevalence": "1/100000", + "Prevalence_details": "Tang et al., 2017: 1/100,000; population specific; frequency of GCN[11] alleles is 1-2% of North America/Europe/Japan (GeneReview)", "STRipy_gene": "PABPN1", "gnomAD_gene": "PABPN1", "GeneReviews": "NBK1126", @@ -2500,9 +2588,11 @@ "pathogenic_max": "33", "ref_copies": "15.7", "repeatunitlen": "3", - "age_onset": "0-20", + "age_onset": "Typical: 0-2 (GeneReview/PMID: 15121777); Range: 0-36 (PMID: 16873766)", "age_onset_min": "0", - "age_onset_max": "20", + "age_onset_max": "36", + "typ_age_onset_min": "0", + "typ_age_onset_max": "2", "novel": "ref", "Mechanism": "Polyalanine", "Mechanism_detail": "Polyalanine", @@ -2512,8 +2602,8 @@ "details": "", "width": "46", "OMIM": "209880", - "Incidence": "", - "Prevalence": "1:148000-200000 births (Estimated)", + "Prevalence": "1/174000", + "Prevalence_details": "1:148000-200000 births (Estimated, may include mild/undiagnosed or be overestimate globally) (GeneReview)", "STRipy_gene": "PHOX2B", "gnomAD_gene": "PHOX2B", "GeneReviews": "NBK1427", @@ -2556,20 +2646,22 @@ "pathogenic_max": "", "ref_copies": "13.7", "repeatunitlen": "3", - "age_onset": "23-87", + "age_onset": "Typical: 57 (PMID: 20399836) - 59 (PMID: 20826197); Range: 23-87 (PMID: 20399836)", "age_onset_min": "23", "age_onset_max": "87", + "typ_age_onset_min": "57", + "typ_age_onset_max": "59", "novel": "ref", "Mechanism": "", "Mechanism_detail": "No information found", "Mechanism_source": "N/A in GeneCard", "source": "PMC2905783, PMID: 20399836, PMID: 10196696", "notes": "Unconfirmed association", - "details": "There is conflicting evidence for the association between this repeat expansion and Parkinson's risk (PMID: 20399836 and PMID: 10196696). Deviation from 10 may impart disease risk with variable penetrance.", + "details": "There is conflicting evidence for the association between this repeat expansion and Parkinson's risk (PMID: 20399836 and PMID: 10196696). Deviation from 10 may impart disease risk with variable penetrance. May be predisposing factor in earlier age of onset in FRDA patients (PMID: 19043662)", "width": "40", "OMIM": "Disease association unclear", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "Unknown", "STRipy_gene": "", "gnomAD_gene": "", "GeneReviews": "", @@ -2612,9 +2704,11 @@ "pathogenic_max": "78", "ref_copies": "10.7", "repeatunitlen": "3", - "age_onset": "8-55", + "age_onset": "Typical: 26-50; Range: 8-56 (OMIM)", "age_onset_min": "8", - "age_onset_max": "55", + "age_onset_max": "56", + "typ_age_onset_min": "26", + "typ_age_onset_max": "50", "novel": "ref", "Mechanism": "Unknown", "Mechanism_detail": "Noted as unknown in literature", @@ -2624,8 +2718,8 @@ "details": "", "width": "31", "OMIM": "604326", - "Incidence": "", - "Prevalence": "Unknown", + "Prevalence": "", + "Prevalence_details": "Unknown. Frequent in India; rare in other places (PMID: 34711523)", "STRipy_gene": "PPP2R2B", "gnomAD_gene": "PPP2R2B", "GeneReviews": "NBK535148", @@ -2668,9 +2762,11 @@ "pathogenic_max": "19", "ref_copies": "12.0", "repeatunitlen": "3", - "age_onset": "0", + "age_onset": "0 (birth)", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "LOF, epigenetic", "Mechanism_detail": "\"mutations abrogated the histone-modifying potential of PRDM12, consistent with a loss of function\"", @@ -2680,8 +2776,8 @@ "details": "", "width": "33", "OMIM": "616488", - "Incidence": "", - "Prevalence": "<1/1,000,000", + "Prevalence": "", + "Prevalence_details": "Found in 2 families. All PRDM12 disease mutations < 1/1,000,000", "STRipy_gene": "PRDM12", "gnomAD_gene": "PRDM12", "GeneReviews": "NBK535148", @@ -2724,9 +2820,11 @@ "pathogenic_max": "", "ref_copies": "", "repeatunitlen": "24", - "age_onset": "middle age", - "age_onset_min": "", - "age_onset_max": "", + "age_onset": "Typical: 50-60 (GeneReview); Range: 31-63 (PMID: 37379724)", + "age_onset_min": "31", + "age_onset_max": "63", + "typ_age_onset_min": "50", + "typ_age_onset_max": "60", "novel": "", "Mechanism": "", "Mechanism_detail": "", @@ -2736,8 +2834,8 @@ "details": "", "width": "", "OMIM": "123400", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "<0.0225/1,000,000: <15% of CJ variants are repeat expansions (NBK535148). 15% newly diagnosed prion disease cases are genetic (GeneReview) 1 individual per million per year worldwide (350 cases annually in US) (PMID: 29939637)\n", "STRipy_gene": "", "gnomAD_gene": "PRNP", "GeneReviews": "NBK1229", @@ -2780,9 +2878,11 @@ "pathogenic_max": "60", "ref_copies": "17.4", "repeatunitlen": "5", - "age_onset": "~18, 23-37", + "age_onset": "Typical: 20-33 (PMID: 30351492); Range: 18 (PMID: 29507423) - 37 (PMID: 30351492)", "age_onset_min": "18", "age_onset_max": "37", + "typ_age_onset_min": "20", + "typ_age_onset_max": "33", "novel": "novel", "Mechanism": "RNA toxicity", "Mechanism_detail": "RNA toxicity hypothesized", @@ -2792,8 +2892,8 @@ "details": "", "width": "91", "OMIM": "618075", - "Incidence": "", - "Prevalence": "~<1/35,000", + "Prevalence": "", + "Prevalence_details": "FAME overall is 1/35,000 in Japan", "STRipy_gene": "RAPGEF2", "gnomAD_gene": "RAPGEF2", "GeneReviews": "NBK535148", @@ -2836,9 +2936,11 @@ "pathogenic_max": "2000", "ref_copies": "11.8", "repeatunitlen": "5", - "age_onset": "33-71", - "age_onset_min": "33", - "age_onset_max": "71", + "age_onset": "Typical: 36-52; Range: 19-76 (GeneReviews)", + "age_onset_min": "19", + "age_onset_max": "76", + "typ_age_onset_min": "36", + "typ_age_onset_max": "52", "novel": "novel", "Mechanism": "", "Mechanism_detail": "No information found", @@ -2848,8 +2950,8 @@ "details": "Pathogenic expansions may be flanked by other motifs. For example, (AAAGG)10-25(AAGGG)exp(AAAGG)4-6 (PMID: 32851396). Motif heterogeneity is common in unaffected individuals", "width": "58", "OMIM": "614575", - "Incidence": "", - "Prevalence": "Unknown, <1/1,000,000", + "Prevalence": "", + "Prevalence_details": "Carrier frequency in European is 0.7-4% and in Chinese Han population is 2.24%; estimated prevalence of 1/20,000 to 1/625 (GeneReview)", "STRipy_gene": "RFC1", "gnomAD_gene": "RFC1", "GeneReviews": "NBK564656", @@ -2892,9 +2994,11 @@ "pathogenic_max": "197", "ref_copies": "11.7", "repeatunitlen": "3", - "age_onset": "", - "age_onset_min": "14", - "age_onset_max": "27", + "age_onset": "Typical: 18-30 (PMID: 35148830); Range: 10-30 (PMID: 35700120)", + "age_onset_min": "10", + "age_onset_max": "30", + "typ_age_onset_min": "18", + "typ_age_onset_max": "30", "novel": "ref", "Mechanism": "Protein toxic GOF", "Mechanism_detail": "toxic gain-of-function mechanism ", @@ -2904,8 +3008,8 @@ "details": "", "width": "35", "OMIM": "", - "Incidence": "", - "Prevalence": "Population dependent", + "Prevalence": "", + "Prevalence_details": "Population dependent. 21.6% of one OPDM cohort (PMID: 35148830)", "STRipy_gene": "RILPL1", "gnomAD_gene": "", "GeneReviews": "", @@ -2948,9 +3052,11 @@ "pathogenic_max": "27", "ref_copies": "15.0", "repeatunitlen": "3", - "age_onset": "0", + "age_onset": "0 (birth) (GeneReviews)", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine", "Mechanism_detail": "Polyalanine", @@ -2960,8 +3066,8 @@ "details": "", "width": "42", "OMIM": "119600", - "Incidence": "", - "Prevalence": "1/1,000,000 births (likely underdiagnosed)", + "Prevalence": "", + "Prevalence_details": "All conditions 1/1,000,000 births (likely underdiagnosed); Utah population frequency 0.12/10,000", "STRipy_gene": "RUNX2", "gnomAD_gene": "RUNX2", "GeneReviews": "NBK1513", @@ -3004,9 +3110,11 @@ "pathogenic_max": "3680", "ref_copies": "21.6", "repeatunitlen": "5", - "age_onset": "18-50", - "age_onset_min": "18", - "age_onset_max": "50", + "age_onset": "Typical: 21-39 (PMID: 29939203); Range: 12 (PMID: 29939203) - 68 (PMID: 29507423)", + "age_onset_min": "12", + "age_onset_max": "68", + "typ_age_onset_min": "21", + "typ_age_onset_max": "39", "novel": "novel", "Mechanism": "RNA toxicity proposed", "Mechanism_detail": "RNA molecules", @@ -3016,8 +3124,8 @@ "details": "", "width": "105", "OMIM": "601068", - "Incidence": "", - "Prevalence": "~<1/35,000", + "Prevalence": "", + "Prevalence_details": "FAME overall is 1/35,000 in Japan", "STRipy_gene": "SAMD12", "gnomAD_gene": "SAMD12", "GeneReviews": "NBK535148", @@ -3060,9 +3168,11 @@ "pathogenic_max": "26", "ref_copies": "15.0", "repeatunitlen": "3", - "age_onset": "Infancy - childhood", + "age_onset": "Typical: 0-3 (PMID: 19654509, PMID: 21289259); Range: 0-9 (PMID: 19654509) ", "age_onset_min": "0", "age_onset_max": "9", + "typ_age_onset_min": "0", + "typ_age_onset_max": "3", "novel": "ref", "Mechanism": "Polyalanine", "Mechanism_detail": "Polyalanine", @@ -3072,8 +3182,8 @@ "details": "", "width": "45", "OMIM": "300123", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "3 families.", "STRipy_gene": "SOX3", "gnomAD_gene": "SOX3", "GeneReviews": "NBK535148", @@ -3116,9 +3226,11 @@ "pathogenic_max": "274", "ref_copies": "11.6", "repeatunitlen": "5", - "age_onset": "mean 25", - "age_onset_min": "5", + "age_onset": "Typical: 12-30; Range: 4-60 (PMID: 31664034)", + "age_onset_min": "4", "age_onset_max": "60", + "typ_age_onset_min": "12", + "typ_age_onset_max": "30", "novel": "novel", "Mechanism": "RNA toxicity", "Mechanism_detail": "RNA toxicity ", @@ -3128,8 +3240,8 @@ "details": "", "width": "54", "OMIM": "607876", - "Incidence": "", - "Prevalence": "~<1/35,000", + "Prevalence": "", + "Prevalence_details": "FAME overall is 1/35,000 in Japan", "STRipy_gene": "STARD7", "gnomAD_gene": "STARD7", "GeneReviews": "NBK535148", @@ -3172,9 +3284,11 @@ "pathogenic_max": "66", "ref_copies": "37.0", "repeatunitlen": "3", - "age_onset": "Most >30", + "age_onset": "Typical: 19-48; Range: 3-62 [has second variant to delay onset] (OMIM)", "age_onset_min": "3", - "age_onset_max": "55", + "age_onset_max": "62", + "typ_age_onset_min": "19", + "typ_age_onset_max": "48", "novel": "ref", "Mechanism": "Polyglutamine ", "Mechanism_detail": "Polyglutamine ", @@ -3184,8 +3298,8 @@ "details": "", "width": "110", "OMIM": "607136", - "Incidence": "", - "Prevalence": "Unknown (global), 0.47:1,000,000 (Japanese)", + "Prevalence": "0.2/100000", + "Prevalence_details": "Unknown (global), <100 families, 0.47:1,000,000 (Japanese), 0.16/100,000 (England) (GeneReview); Tang et al., 2017: 0.2/100,000", "STRipy_gene": "TBP", "gnomAD_gene": "TBP", "GeneReviews": "NBK1438", @@ -3231,6 +3345,8 @@ "age_onset": "0", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine", "Mechanism_detail": "Polyalanine", @@ -3240,8 +3356,8 @@ "details": "", "width": "45", "OMIM": "187500", - "Incidence": "", - "Prevalence": "Unknown for specific gene", + "Prevalence": "", + "Prevalence_details": "1 individual with STR mutation (GeneReview)", "STRipy_gene": "TBX1", "gnomAD_gene": "TBX1", "GeneReviews": "NBK535148", @@ -3284,20 +3400,22 @@ "pathogenic_max": "150", "ref_copies": "25.3", "repeatunitlen": "3", - "age_onset": "~40", + "age_onset": "Typical: 40-59 (PMID: 1676829); Range: 32 (PMID: 21245398) - 70 (PMID: 25168903)", "age_onset_min": "32", "age_onset_max": "70", + "typ_age_onset_min": "40", + "typ_age_onset_max": "59", "novel": "ref", "Mechanism": "RNA toxicity proposed", "Mechanism_detail": "\"sequestration of MBNL1 in RNA foci, similar to the mechanism underlying myotonic dystrophy-1 \"", "Mechanism_source": "(10.1074/jbc.M114.621607)", "source": "Pathogenic Short Tandem Repeats Gnomad v3.1.2, NBK535148", "notes": "", - "details": "", + "details": "Penetrance is <100%; reduced penetrance has been reported in individuals with >80 CTG repeats [Wieben et al 2014]. Predominantly in women (~75%) (PMID: 16769829). \u201cAlthough studies on the prevalence of FECD worldwide are limited, the disorder is thought to be more common in Eurasian populations, with its corneal manifestations documented in 11% of females and 7% of males in Reykjavik, Iceland,3 8.5 % of Singapore Chinese,4 and 5.5% of Japanese.4 (PMID: 25722209) ", "width": "72", "OMIM": "613267", - "Incidence": "", - "Prevalence": "~4/100 (over 40)", + "Prevalence": "4.5/100", + "Prevalence_details": "~4/100 (over 40) (OMIM); 5/100 (PMID: 20825314)", "STRipy_gene": "TCF4", "gnomAD_gene": "TCF4", "GeneReviews": "NBK535148", @@ -3340,9 +3458,11 @@ "pathogenic_max": "100", "ref_copies": "29.3", "repeatunitlen": "3", - "age_onset": "Median age of onset was 34 (range, 4\u201351)", + "age_onset": "Typical: 8-40; Range: 4-51 (PMID: 37148549)", "age_onset_min": "4", "age_onset_max": "51", + "typ_age_onset_min": "8", + "typ_age_onset_max": "40", "novel": "ref", "Mechanism": "PolyQ toxicity", "Mechanism_detail": "", @@ -3352,8 +3472,8 @@ "details": "Expansion found in affected individuals from 2 families and not in 500 controls. Longer alleles were associated wither earlier age of onset. For example, an individual with 100 repeats had age of onset at 4 years.", "width": "", "OMIM": "", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "Unknown", "STRipy_gene": "", "gnomAD_gene": "", "GeneReviews": "", @@ -3396,9 +3516,11 @@ "pathogenic_max": "1100", "ref_copies": "18.8", "repeatunitlen": "3", - "age_onset": "20s-70s", - "age_onset_min": "20", - "age_onset_max": "70", + "age_onset": "Limited clinical details from one family, \"early 20s to 70s\"", + "age_onset_min": "23", + "age_onset_max": "74", + "typ_age_onset_min": "23", + "typ_age_onset_max": "74", "novel": "novel", "Mechanism": "RNA toxicity", "Mechanism_detail": "RNA toxicity hypothesized", @@ -3408,8 +3530,8 @@ "details": "", "width": "93", "OMIM": "618074", - "Incidence": "", - "Prevalence": "~<1/35,000", + "Prevalence": "", + "Prevalence_details": "FAME overall is 1/35,000 in Japan", "STRipy_gene": "TNRC6A", "gnomAD_gene": "TNRC6A", "GeneReviews": "NBK535148", @@ -3452,9 +3574,11 @@ "pathogenic_max": "3", "ref_copies": "", "repeatunitlen": "10", - "age_onset": "<10", - "age_onset_min": "", + "age_onset": "Typical: 1-3 (PMID: 33559681); Range: 0-10 (OMIM)", + "age_onset_min": "0", "age_onset_max": "10", + "typ_age_onset_min": "1", + "typ_age_onset_max": "3", "novel": "", "Mechanism": "", "Mechanism_detail": "", @@ -3464,8 +3588,8 @@ "details": "Any deviation from 2 motifs is thought to be pathogenic", "width": "", "OMIM": "619216", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "Biallelic variants found in 0.01% of 100 KGP participants; enriched in those with motor disease. 80% of VWA1 pathogenic variants are expansions/contractions (GeneReview)", "STRipy_gene": "", "gnomAD_gene": "VWA1", "GeneReviews": "NBK535148", @@ -3508,9 +3632,11 @@ "pathogenic_max": "110", "ref_copies": "0.0", "repeatunitlen": "3", - "age_onset": "0", + "age_onset": "0 (birth)", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Methylation", "Mechanism_detail": "Methylation", @@ -3520,8 +3646,8 @@ "details": "", "width": "1", "OMIM": "615777", - "Incidence": "", - "Prevalence": "<1 / 1,000,000 births", + "Prevalence": "", + "Prevalence_details": "<1 / 1,000,000 births (orphanet); \u00bd of DBQD variants (GeneReview). <50 DBQD cases", "STRipy_gene": "XYLT1", "gnomAD_gene": "XYLT1", "GeneReviews": "NBK535148", @@ -3564,9 +3690,11 @@ "pathogenic_max": "1000", "ref_copies": "10.0", "repeatunitlen": "5", - "age_onset": "19.5 years (range 10-33) for tremor and 25 years (range 19-33) for seizures", + "age_onset": "Typical: 20-25 (PMID: 22713812); Range: 10-33 (PMID: 31539032)", "age_onset_min": "10", "age_onset_max": "33", + "typ_age_onset_min": "20", + "typ_age_onset_max": "25", "novel": "novel", "Mechanism": "RNA toxicity", "Mechanism_detail": "RNA toxicity hypothesized", @@ -3576,8 +3704,8 @@ "details": "", "width": "34", "OMIM": "615127", - "Incidence": "", - "Prevalence": "~<1/35,000", + "Prevalence": "", + "Prevalence_details": "FAME overall is 1/35,000 in Japan", "STRipy_gene": "YEATS2", "gnomAD_gene": "YEATS2", "GeneReviews": "NBK535148", @@ -3620,20 +3748,22 @@ "pathogenic_max": "64", "ref_copies": "21.3", "repeatunitlen": "3", - "age_onset": "Average 56.4 years. Range 20-60 years", - "age_onset_min": "20", + "age_onset": "Typical: 37- 56; Range: 15 - 60 (PMID: 38035881 - https://doi.org/10.1101/2023.10.03.23296230) ", + "age_onset_min": "15", "age_onset_max": "60", + "typ_age_onset_min": "37", + "typ_age_onset_max": "56", "novel": "ref", "Mechanism": "", "Mechanism_detail": "", "Mechanism_source": "", "source": "https://doi.org/10.1101/2023.10.03.23296230", "notes": "", - "details": "Expansion found in affected individuals from 3 families and not in any of the 1001 controls", + "details": "Expansion found in affected individuals from 3 families and not in any of the 1001 controls. Possible anticipation (PMID: 38197134, PMID: 38035881)", "width": "", "OMIM": "600223", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "Unknown", "STRipy_gene": "", "gnomAD_gene": "", "GeneReviews": "", @@ -3679,6 +3809,8 @@ "age_onset": "0", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine ", "Mechanism_detail": "Polyalanine ", @@ -3688,11 +3820,11 @@ "details": "", "width": "45", "OMIM": "609637", - "Incidence": "", - "Prevalence": "Unknown ZIC2 specific", + "Prevalence": "1.4/1000000", + "Prevalence_details": "0.05-0.23/100,000; math done by 40% of pathogenic variants in ZIC2 are expansion (GeneReview); 5% of non-syndromic HPE are ZIC2 gene (NBK1530), and nonsyndromic HPE is [25]-50% of HPE, which affects 1/10,000 newborns (Medline non-syndromic HPE) - ZIC2 is 9.2% of HPE cases, whicho ccur in 1/16,000 live births (PMID: 17274816)", "STRipy_gene": "ZIC2", "gnomAD_gene": "ZIC2", - "GeneReviews": "NBK535148", + "GeneReviews": "NBK1530", "Year": "2001" }, { @@ -3735,6 +3867,8 @@ "age_onset": "0", "age_onset_min": "0", "age_onset_max": "0", + "typ_age_onset_min": "0", + "typ_age_onset_max": "0", "novel": "ref", "Mechanism": "Polyalanine", "Mechanism_detail": "Polyalanine", @@ -3744,8 +3878,8 @@ "details": "", "width": "30", "OMIM": "314390", - "Incidence": "", - "Prevalence": "Unknown", + "Prevalence": "", + "Prevalence_details": "1 patient with VACTERL died at birth. 8 patients with X-linked OAVS at 11 motifs; 1 individual in OAVS cohort with 12 repeats. ", "STRipy_gene": "ZIC3", "gnomAD_gene": "ZIC3", "GeneReviews": "NBK535148", @@ -3788,9 +3922,11 @@ "pathogenic_max": "450", "ref_copies": "13.0", "repeatunitlen": "3", - "age_onset": "", - "age_onset_min": "", - "age_onset_max": "", + "age_onset": "2-3 (four individuals; PMID: 25196122)", + "age_onset_min": "2", + "age_onset_max": "3", + "typ_age_onset_min": "2", + "typ_age_onset_max": "3", "novel": "ref", "Mechanism": "Methylation", "Mechanism_detail": "Methylation", @@ -3800,8 +3936,8 @@ "details": "", "width": "38", "OMIM": "616181", - "Incidence": "", "Prevalence": "", + "Prevalence_details": "4 individuals", "STRipy_gene": "", "gnomAD_gene": "", "GeneReviews": "",