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.3382G>A (p.Ala1128Thr)

CA013661

42959 (ClinVar)

Gene: MYH7

Condition: cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: dc6a24be-6cd7-45ac-a097-1d5031608aa7

Approved on: 2021-03-22

Published on: 2021-08-25

HGVS expressions

NM_000257.3:c.3382G>A

NM_000257.3(MYH7):c.3382G>A (p.Ala1128Thr)

ENST00000355349.4:c.3382G>A

ENST00000355349.3:c.3382G>A

NM_000257.4:c.3382G>A

NC_000014.9:g.23420189C>T

CM000676.2:g.23420189C>T

NC_000014.8:g.23889398C>T

CM000676.1:g.23889398C>T

NC_000014.7:g.22959238C>T

NG_007884.1:g.20473G>A

Likely Benign

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

BS1

PS4 PP3 PM2

Evidence Links 0

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

The c.3382G>A (p.Ala1128Thr) variant in MYH7 has been identified in 0.02% (FAF 95% CI; 10/34232) of Latino chromosomes in gnomAD v2.1.1 (https://gnomad.broadinstitute.org), which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BS1; Kelly 2018 PMID:29300372). Allowing a variant to reach a likely benign classification based on BS1 alone represents a revision of the original ACMG/AMP framework by ClinGen’s Sequence Variant Interpretation Working Group (Tavtigian 2018 PMID: 29300386). In summary, this variant meets criteria to be classified as likely benign for cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): BS1

BS1

has been identified in 0.02 (0.016)% (FAF 95% CI; 10/34323) of East Asian chromosomes in gnomAD v2.1.1 (https://gnomad.broadinstitute.org), which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BS1; PMID:29300372). Pan ethnic chrom 27/240554, also FAF 0.016%

PS4

Variant identified in 3 probands with DCM- but variant did not meet PM2 criteria

PP3

comp tools mixed

PM2

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.