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.788T>C (p.Ile263Thr)

CA016824

43106 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: da0ede45-78bd-43e3-8f1f-9ac160621dc4

HGVS expressions

NM_000257.3:c.788T>C

NM_000257.3(MYH7):c.788T>C (p.Ile263Thr)

NC_000014.9:g.23431426A>G

CM000676.2:g.23431426A>G

NC_000014.8:g.23900635A>G

CM000676.1:g.23900635A>G

NC_000014.7:g.22970475A>G

NG_007884.1:g.9236T>C

NM_000257.4:c.788T>C

ENST00000355349.3:c.788T>C

Pathogenic

PS4 PP3 PM2 PM1 PP1_Strong

Evidence Links 2

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.788T>C (p.Ile263Thr) variant in MYH7 has been reported in >20 individuals with hypertrophic cardiomyopathy (PS4: PMID:15008060; PMID:9829907; PMID:12707239; PMID:22429680; PMID:20624503; Partners LMM ClinVar SCV000059656.5; SHaRe consortium, PMID: 30297972). This variant segregated with disease in 10 affected individuals (PP1_Strong: PMID:15008060; PMID:9829907). 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). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3). 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, PP1_Strong, PM1, PM2, PP3

PS4

Variant identified in >20 unrelated individuals with HCM (including counts from ClinVar SCV000059656.5; SHaRe and UK data)

PP3

Tool suggest damaging

PM2

Absent from ExAC

PM1

Variant located in the head domain

PP1_Strong

>10 segregations with disease across 3 families total

Segregation in two families. In Family1, segregated with disease in 8 affected family members. In Family2, segregated with disease in 1 affected family member PubMed:15008060

Variant segregated with disease in 1 affected family member PubMed:9829907

Approved on: 2016-12-15

Published on: 2018-11-16

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