ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4992C>A (p.Asn1664Lys) (rs763538103)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000777755 SCV000913718 uncertain significance Cardiomyopathy 2018-05-29 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the coiled-coil LMM domain of the MYH7 protein, a C-terminal tail region that forms the thick filament backbone and interacts with other proteins. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact the RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in one individual with hypertrophic cardiomyopathy in the literature (PMID: 27247418). This variant is rare in the general population and has been identified in 3/246220 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Invitae RCV000554994 SCV000623729 uncertain significance Hypertrophic cardiomyopathy 2017-05-20 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 1664 of the MYH7 protein (p.Asn1664Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs763538103, ExAC 0.009%). This variant has been reported in the literature in individuals affected with hypertrophic cardiomyopathy (PMID: 27247418). ClinVar contains an entry for this variant (Variation ID: 217461). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be tolerated. The algorithm has a sensitivity of 94% and a specificity of 89% (PMID: 21310275). In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory of Genetics and Molecular Cardiology,University of São Paulo RCV000201468 SCV000256129 likely pathogenic Familial hypertrophic cardiomyopathy 1 criteria provided, single submitter clinical testing

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