ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1405G>T (p.Asp469Tyr)

dbSNP: rs397516106
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000804896 SCV000944834 uncertain significance Hypertrophic cardiomyopathy 2025-01-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 469 of the MYH7 protein (p.Asp469Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 22464770, 27532257, 37652022). ClinVar contains an entry for this variant (Variation ID: 42844). 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 disruptive. This variant is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). 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 Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852456 SCV000995149 uncertain significance Cardiomyopathy 2019-01-24 criteria provided, single submitter clinical testing
3billion RCV003313931 SCV004013609 likely pathogenic Dilated cardiomyopathy 1S criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PMID:. 29300372. Predicted Consequence/Location:). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.81; 3Cnet: 0.93). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with MYH7 related disorder (PMID: 22464770). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx RCV004786300 SCV005401183 uncertain significance not provided 2024-05-13 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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: 27532257, 29300372, 22464770, 37652022)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035724 SCV000059375 uncertain significance not specified 2014-01-02 no assertion criteria provided clinical testing proposed classification - variant undergoing re-assessment, contact laboratory

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