ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.4328C>A (p.Ala1443Asp) (rs727503234)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000151213 SCV000199051 uncertain significance not specified 2013-11-01 criteria provided, single submitter clinical testing The Ala1443Asp variant in MYH6 has been reported in 1 individual with congenital heart disease (ASD) and was absent from at least 960 control chromosomes (Grana dos-Riveron 2010, Granados-Riveron 2012). It was also absent from large populati on studies. Computational analyses (biochemical amino acid properties, conservat ion, AlignGVGD, PolyPhen2, and SIFT) suggest that this variant may impact the pr otein, though this information is not predictive enough to determine pathogenici ty. In summary, additional information is needed to fully assess the clinical si gnificance of this variant.
Invitae RCV000701551 SCV000830355 uncertain significance Familial hypertrophic cardiomyopathy 14 2018-01-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 1443 of the MYH6 protein (p.Ala1443Asp). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is present in population databases (rs727503234, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in the literature in an individual affected with an atrial septal defect and his unaffected mother, and in individuals affected with dilated cardiomyopathy (PMID: 20656787, 28416588, 24082139) ClinVar contains an entry for this variant (Variation ID: 164221). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Center for Human Genetics,University of Leuven RCV000768516 SCV000886829 uncertain significance Hypertrophic cardiomyopathy 2018-10-31 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000761595 SCV000891756 uncertain significance Atrial septal defect 3 2018-07-12 criteria provided, single submitter research
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845518 SCV000987621 uncertain significance Primary familial hypertrophic cardiomyopathy criteria provided, single submitter clinical testing
Blueprint Genetics RCV000157341 SCV000207078 uncertain significance Primary dilated cardiomyopathy 2014-09-29 no assertion criteria provided clinical testing

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