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]

Variant: NM_000257.3(MYH7):c.4909G>A (p.Ala1637Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA015454

43044 (ClinVar)

Gene: MYH7

Condition: cardiomyopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: ccdf0002-db7d-4fd8-989a-73c765052ee9

Approved on: 2021-03-22

Published on: 2021-08-25

HGVS expressions

NM_000257.3:c.4909G>A

NM_000257.3(MYH7):c.4909G>A (p.Ala1637Thr)

ENST00000355349.4:c.4909G>A

ENST00000355349.3:c.4909G>A

NR_126491.1:n.309C>T

NM_000257.4:c.4909G>A

NC_000014.9:g.23416048C>T

CM000676.2:g.23416048C>T

NC_000014.8:g.23885257C>T

CM000676.1:g.23885257C>T

NC_000014.7:g.22955097C>T

NG_007884.1:g.24614G>A

Likely Benign

BS1 BP4

PS4 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.4909G>A (p.Ala1637Thr) variant in MYH7 has been observed in 0.060% (FAF 95% CI; 22/24960) of African chromosomes in gnomAD v2.1.1 (http://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). Additionally, computational prediction tools and conservation analysis suggest that this variant may not impact the protein (BP4). 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, BP4

BS1

Observed in 0.088% (22/24960; FAF 0.060%, 95% CI) of African chromosomes in gnomAD v2.1.1

BP4

All tool in Alamut other than MutationTaster call benign (AlignGVGD, SIFT, PolyPhen2 & Sarcomere PolyPhen). Additionally, this position is not completely conserved in mammals, 5 of which carry this amino acid change.

PS4

LMM: 2 individuals with cardiomyopathy (PMID:20624503; Partners LMM ClinVar SCV000059589.5) Invitae: Seen in 1 distal myopathy and 3 DCM Ingles: 1 family that does not have HCM Ambry: 1 proband with HCM, 1 with DCM, 1 person who died in police custody, and 1 proband with "heart disease" and no other info who also carried 2 other variants (TTR p.V142I and TRDN p.D18Afs) ARUP: 25 yo email with non-ischemic cardiomyopathy

PM2

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

Curation History

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