ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3581C>T (p.Ala1194Val)

gnomAD frequency: 0.00004  dbSNP: rs730880594
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158244 SCV000208179 uncertain significance not provided 2024-10-03 criteria provided, single submitter clinical testing Identified in a cohort of patients with HCM in published literature (PMID: 31199839); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28679633, 31199839)
Labcorp Genetics (formerly Invitae), Labcorp RCV000461779 SCV000546456 likely benign Hypertrophic cardiomyopathy 2025-01-21 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001191619 SCV001359505 likely benign Cardiomyopathy 2021-04-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002460049 SCV002618089 likely benign Cardiovascular phenotype 2022-01-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000223738 SCV000280264 uncertain significance not specified 2013-08-01 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. MYBPC3 p.Ala1194Val This variant is novel; it has not been reported in association with cardiomyopathy or in healthy controls. This is a conservative amino acid change with the replacement of nonpolar Alanine with a nonpolar Valine. Alanine is highly conserved at this residue and in silico analysis (PolyPhen2) predicts the amino acid change to be probably damaging to protein structure and function. Richard et al (2003) reported a variant at the same codon (p.Ala1194Thr) in an individual with severe wall thickness (>13mm) and HCM. Richard et al did not find that variant in 200 control individuals. Disease associated variants have been reported in nearby codons as well (Leu187Arg, Leu1200Pro) (Human Gene Mutation Database http://www.hgmd.org/). It is not listed in dbSNP. There is insufficient data to determine whether or not this variant causes cardiomyopathy.

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