Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000257.3(MYH7):c.2207T>C (p.Ile736Thr)

Curation History

CA011970

164342 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e08a8c4f-f972-4f81-80b1-528cd4e6ca91

Approved on: 2016-12-15

Published on: 2018-11-16

HGVS expressions

NM_000257.3:c.2207T>C

NM_000257.3(MYH7):c.2207T>C (p.Ile736Thr)

NM_000257.4:c.2207T>C

ENST00000355349.3:c.2207T>C

NC_000014.9:g.23425774A>G

CM000676.2:g.23425774A>G

NC_000014.8:g.23894983A>G

CM000676.1:g.23894983A>G

NC_000014.7:g.22964823A>G

NG_007884.1:g.14888T>C

Pathogenic

PS4 PP1_Moderate PM2 PM1

Evidence Links 7

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.2207T>C (p.Ile736Thr) variant in MYH7 has been reported in >20 individuals with hypertrophic cardiomyopathy (PS4; PMID:16630449; PMID:12974739; PMID:16199542; PMID:15856146; PMID:17125710; PMID:20738943; SHaRe consortium, PMID: 30297972; Partners LMM ClinVar SCV000199207.4; AGCMC Sydney ClinVar SCV000212631.2). This variant segregated with disease in 5 affected individuals (PP1_Moderate; PMID:15856146; PMID:17125710; Partners LMM ClinVar SCV000199207.4). This variant was absent from large population studies (PM2; http://exac.broadinstitute.org). This variant lies in the head region of the protein (aa 181-937) and missense variants in this region are statistically more likely to be disease-associated (PM1; PMID:27532257). In summary, this variant meets criteria to be classified as pathogenic for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PS4; PM1; PM2; PP1_Moderate

PS4

>20 probands with HCM including SHaRe data; ClinVar SCV000199207.4; ClinVar SCV000212631.2

Variant identified in 1 proband with HCM PubMed:20738943

Variant identified in 1 proband with HCM PubMed:15856146

Variant identified in 2 probands with HCM PubMed:17125710

Variant identified in 1 proband with HCM PubMed:12974739

Variant identified in 1 proband with HCM PubMed:16630449

Variant identified in 1 proband with HCM PubMed:16199542

Variant identified in 6 probands with HCM PubMed:27532257

PP1_Moderate

5 segregations including ClinVar SCV000199207.4

Variant segregated with disease in 2 affected family members PubMed:15856146

Variant segregated with disease in 2 affected family members PubMed:17125710

PM2

Absent from ExAC

PM1

Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated

Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated PubMed:27532257

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.