Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • See Evidence submitted by expert panel for details.

Variant: NM_000257.4(MYH7):c.3337G>A (p.Ala1113Thr)

CA013599

36638 (ClinVar)

Gene: MYH7
Condition: hypertrophic cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 101ed835-970e-4785-ab2f-227cfeb92d31
Approved on: 2021-03-22
Published on: 2021-08-25

HGVS expressions

NM_000257.4:c.3337G>A
NM_000257.4(MYH7):c.3337G>A (p.Ala1113Thr)
ENST00000355349.4:c.3337G>A
ENST00000355349.3:c.3337G>A
NM_000257.3:c.3337G>A
NC_000014.9:g.23420234C>T
CM000676.2:g.23420234C>T
NC_000014.8:g.23889443C>T
CM000676.1:g.23889443C>T
NC_000014.7:g.22959283C>T
NG_007884.1:g.20428G>A
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Uncertain Significance

Met criteria codes 2
PS4_Moderate PM2
Not Met criteria codes 17
PVS1 BA1 BS4 BS3 BS1 BP3 BP7 BP4 PS3 PS2 PS1 PP1 PP3 PM6 PM1 PM4 PM5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
The c.3337G>A (p.Ala1113Thr) variant in MYH7 has been identified in 6 individuals with HCM (PS4_Moderate; GeneDx pers. comm.; Invitae pers. comm.; OMGL pers. comm.). This variant was absent from large population studies (PM2; http://gnomad.broadinstitute.org, v.2.1.1). Computational prediction tools and conservation analysis were mixed about the potential impact of this variant. In summary, due to insufficient evidence, this variant is classified as uncertain significance for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PS4_Moderate; PM2
Met criteria codes
PS4_Moderate
This variant has been identified in 6 individuals with HCM (PS4_Moderate; GeneDx pers comm; Invitae pers comm; OMGL pers comm). No literature found via Alamut search string in Google Scholar or HGMD GeneDx 3 HCM Invitae 2 HCM OMGL 1 HCM
PM2
Absent from gnomAD with ~65x on exomes and ~30x on genomes.
Not Met criteria codes
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No segregation evidence
BS3
No functional evidence
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No functional evidence
PS2
No de novo evidence
PS1
No other variants at this codon in ClinVar or HGMD.
PP1
No segregation evidence
PP3
Sarcomere PolyPhen predicts pathogenic (PMID21310275). Other tools are mixed.
PM6
No de novo evidence
PM1
Variant is outside designated cluster domain.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No other variants at this codon in ClinVar or HGMD.
Curation History
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