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]

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

CA011970

164342 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

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

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 PM2 PM1 PP1_Moderate

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

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

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

Approved on: 2016-12-15

Published on: 2018-11-16

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