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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000257.3(MYH7):c.1594T>C (p.Ser532Pro)

CA011011

14108 (ClinVar)

Gene: MYH7

Condition: dilated cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 9486153c-4de2-4686-927c-cbe960ccbc06

HGVS expressions

NM_000257.3:c.1594T>C

NM_000257.3(MYH7):c.1594T>C (p.Ser532Pro)

NC_000014.9:g.23427879A>G

CM000676.2:g.23427879A>G

NC_000014.8:g.23897088A>G

CM000676.1:g.23897088A>G

NC_000014.7:g.22966928A>G

NG_007884.1:g.12783T>C

NM_000257.4:c.1594T>C

ENST00000355349.3:c.1594T>C

Pathogenic

PS4_Supporting PS3 PP3 PM2 PM1 PP1_Strong

Evidence Links 6

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.1594T>C (p.Ser532Pro) variant in MYH7 has been reported in 2 individuals with dilated cardiomyopathy (PS4_Supporting; PMID:11106718; PMID:22949430; Partners LMM ClinVar SCV000199219.4). This variant segregated with disease in >10 affected individuals (PP1_Strong; PMID:11106718; PMID:22949430). Mouse model indicates that this variant disrupts the function of MYH7 and leads to a phenotype consistent with DCM (PS3; PMID:16983074; PMID:23313350; PMID:17351073 ). 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 dilated cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PS3; PP1_ Strong; PM1; PM2; PP3; PS4_Supporting

PS4_Supporting

Variant identified in 2 probands with DCM (including ClinVar SCV000199219.4)

Variant identified in case with DCM (may be same case as Lakdawala et al) PubMed:11106718

Variant identified in case with DCM (may be same case as Kamisago et al) PubMed:22949430

PS3

Mouse model indicates that this variant disrupts the function of MYH7 and leads to a phenotype consistent with DCM

mouse model indicates that this variant disrupts the function of MYH7 and leads to a phenotype consistent with DCM PubMed:16983074

mouse model indicates that this variant disrupts the function of MYH7 and leads to a phenotype consistent with DCM PubMed:17351073

mouse model indicates that this variant disrupts the function of MYH7 and leads to a phenotype consistent with DCM PubMed:23313350

PP3

Tools predict damaging

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:2753225

PP1_Strong

>10 segregations

Variant segregated with disease in 16 affected family members (may be same case as Lakdawala et al) PubMed:11106718

Variant segregated with disease in 7 affected family members (may be same case as Kamisago et al) PubMed:22949430

Approved on: 2016-12-15

Published on: 2018-11-16

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.