ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.1002T>A (p.Asp334Glu)

gnomAD frequency: 0.00008  dbSNP: rs371859345
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000217101 SCV000272013 uncertain significance not specified 2015-02-12 criteria provided, single submitter clinical testing The p.Asp334Glu variant in MYH6 has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/10340 African chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs3 71859345). Computational prediction tools and conservation analysis do not provi de strong support for or against and impact to the protein. This variant is loca ted in the last three bases of the exon, which is part of the 5? splice region; however, computational tools do not suggest an impact to splicing. This informat ion is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Asp334Glu variant is uncertain.
Invitae RCV000539441 SCV000648215 uncertain significance Hypertrophic cardiomyopathy 14 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 334 of the MYH6 protein (p.Asp334Glu). This variant is present in population databases (rs371859345, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 228883). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000217101 SCV002500118 uncertain significance not specified 2022-03-05 criteria provided, single submitter clinical testing
GeneDx RCV002293427 SCV002586617 uncertain significance not provided 2022-10-11 criteria provided, single submitter clinical testing Reported in association with HCM in published literature (Ingles et al., 2019); 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: 30681346)
Ambry Genetics RCV002390582 SCV002696958 uncertain significance Cardiovascular phenotype 2022-05-04 criteria provided, single submitter clinical testing The p.D334E variant (also known as c.1002T>A), located in coding exon 9 of the MYH6 gene, results from a T to A substitution at nucleotide position 1002. The aspartic acid at codon 334 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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