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.3981C>A (p.Asn1327Lys)

CA014310

36641 (ClinVar)

Gene: MYH7

Condition: hypertrophic cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6b897fc5-b902-4fac-adc3-ad57632dacad

Approved on: 2020-04-24

Published on: 2021-06-16

HGVS expressions

NM_000257.3:c.3981C>A

NM_000257.3(MYH7):c.3981C>A (p.Asn1327Lys)

ENST00000355349.4:c.3981C>A

ENST00000355349.3:c.3981C>A

NM_000257.4:c.3981C>A

NC_000014.9:g.23418398G>T

CM000676.2:g.23418398G>T

NC_000014.8:g.23887607G>T

CM000676.1:g.23887607G>T

NC_000014.7:g.22957447G>T

NG_007884.1:g.22264C>A

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Benign"

BA1 BS4

BP4 PS4 PP3 PM2 BS1

Evidence Links 2

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.3981C>A (p.Asn1327Lys) variant in MYH7 has been identified in 0.16% (FAF 95% CI; 24/10156) of Ashkenazi Jewish chromosomes in gnomAD v2.1.1 (https://gnomad.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; Kelly 2018 PMID:29300372). Based on criteria selected, this variant should be classified as benign; however, the expert panel felt that since frequency in other populations is not as elevated as in the Ashkenazi Jewish population, it warrants adjusting in the final classification to likely benign. Therefore, this variant is classified as likely benign for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): BA1 with expert panel adjustment.

BA1

This variant has been identified in 0.16% (FAF 95% CI; 24/10156) of Ashkenazi Jewish chromosomes in gnomAD v2.1.1 (https://gnomad.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372).

BS4

3 non-segregations total (phenotype positive; genotype negative) including ClinVar SCV000059529.5

An affected relative of proband had HCM but did not carry MYH7 variant PubMed:15483641

BP4

tools conflicting

PS4

>15 probands with HCM identified (including ClinVar SCV000059529.5, ClinVar SCV000254446.5, and SHaRe data) however PS4 not applied as PM2 criterion was not met

Variant identified in 2 probands with HCM PubMed:27532257

Variant identified in proband with HCM PubMed:15483641

PP3

tools conflicting

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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