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.511A>C (p.Asn171His)

CA015706

181310 (ClinVar)

Gene: MYH7
Condition: hypertrophic cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e4f58ef5-c2b1-4be7-9ff6-119d18d9ad29
Approved on: 2021-11-19
Published on: 2021-12-09

HGVS expressions

NM_000257.4:c.511A>C
NM_000257.4(MYH7):c.511A>C (p.Asn171His)
NC_000014.9:g.23432498T>G
CM000676.2:g.23432498T>G
NC_000014.8:g.23901707T>G
CM000676.1:g.23901707T>G
NC_000014.7:g.22971547T>G
NG_007884.1:g.8164A>C
ENST00000355349.4:c.511A>C
ENST00000355349.3:c.511A>C
NM_000257.3:c.511A>C
More

Uncertain Significance

Met criteria codes 2
PP3 PM2
Not Met criteria codes 10
PS2 PS4 PS1 PP1 PM6 PM1 PM5 BA1 BS4 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
The NM_000257.4(MYH7):c.511A>C (p.Asn171His) variant has been identified in 1 individual with HCM (GeneDx pers. comm.), however, this data is insufficient to apply the PS4 criterion. This variant was absent from large population studies (PM2; gnomAD v2.1.1, http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3). 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): PM2, PP3.
Met criteria codes
PP3
REVEL meta-predictor score is 0.826, impact threshold > 0.75. Multiple predictors predict that this missense change is deleterious.
PM2
absent from gnomAD with good coverage on exomes and genomes (~90x & 30x)
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
Only 1 HCM proband observed
PS1
No other pathogenic variant established with same protein effect
PP1
No papers for this variant in literature and no segregation data from clinical labs.
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not in mutation hotspot (p.181-937)
PM5
No other pathogenic missense seen at this codon
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No papers for this variant in literature and no segregation data from clinical labs.
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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