ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2451C>A (p.Asn817Lys) (rs876661372)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001051002 SCV001215135 uncertain significance Hypertrophic cardiomyopathy 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 817 of the MYH7 protein (p.Asn817Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hypertrophic cardiomyopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 235029). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000223901 SCV000280323 uncertain significance not specified 2012-01-14 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. MYH7 p.Asn817Lys (c.2451C>A) ***Only brief review done, for SHaRe. Correlagen classifies this variant as possibly associated. Given the lack of case data we consider this variant a variant of uncertain significance. There is no ClinVar entry. In silico analysis with mutationtaster predicts the variant to be disease causing. The asparagine at codon 817 is conserved across species, as are neighboring amino acids. There is no variation at codon 817 listed in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of ***). ***consider adding numbers for each ancestry group

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