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.2146G>A (p.Gly716Arg)

CA011770

14105 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 768afef8-4fb0-47f1-980f-d95c2ab71447

HGVS expressions

NM_000257.3:c.2146G>A

NM_000257.3(MYH7):c.2146G>A (p.Gly716Arg)

NM_000257.4:c.2146G>A

ENST00000355349.3:c.2146G>A

NC_000014.9:g.23425980C>T

CM000676.2:g.23425980C>T

NC_000014.8:g.23895189C>T

CM000676.1:g.23895189C>T

NC_000014.7:g.22965029C>T

NG_007884.1:g.14682G>A

Pathogenic

PM2 PM1 PM6 PP1_Strong PS4 PP3

Evidence Links 9

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.2146G>A (p.Gly716Arg) variant in MYH7 has been reported in >30 individuals with hypertrophic cardiomyopathy (PS4; PMID:23074333; PMID:20641121; PMID:12084606; PMID:8282798; PMID:18953637; PMID:12707239; PMID:15358028; PMID:12975413; Partners LMM ClinVar SCV000059418.5; SHaRe consortium, PMID: 30297972). This variant has been identified as a de novo occurrence in 2 probands with hypertrophic cardiomyopathy (PM6; PMID:18953637; Partners LMM ClinVar SCV000059418.5). This variant segregated with disease in 11 affected individuals (PP1_Strong; PMID:8282798; PMID:20641121; Partners LMM ClinVar SCV000059418.5). 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; PM6; PP3

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

PM6

2 de novo occurrences (including ClinVar SCV000059418.5)

de novo occurrence in proband with HCM PubMed:18953637

PP1_Strong

11 segregations (including ClinVar SCV000059418.5)

Variant segregated with disease in 6 family members PubMed:20641121

Variant segregated with disease in 2 affected family members PubMed:8282798

PS4

>30 probands with HCM (including SHaRe data and ClinVar SCV000059418.5)

Variant identified in 1 proband with HCM PubMed:12084606

Variant identified in 9 probands PubMed:23074333

Variant identified in 2 probands with HCM PubMed:12975413

Variant identified in 1 proband PubMed:20641121

Variant identified in 1 proband with HCM PubMed:15358028

Variant identified in 2 probands with HCM PubMed:12707239

Variant identified de novo in 1 proband with HCM PubMed:18953637

Variant identified in 1 proband with HCM PubMed:8282798

PP3

Tools suggest impact

Approved on: 2016-12-15

Published on: 2018-11-16

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