ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1544T>G (p.Met515Arg) (rs863224900)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000461645 SCV000546227 likely pathogenic Hypertrophic cardiomyopathy 2017-03-13 criteria provided, single submitter clinical testing This sequence change replaces methionine with arginine at codon 515 of the MYH7 protein (p.Met515Arg). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 15358028, Invitae). 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). A computational algorithm designed to assess the pathogenicity of variants in MYH7 with regard to hypertrophic cardiomyopathy predicted this sequence change to be deleterious. 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 absent from population databases, was previously described in individuals with hypertrophic cardiomyopathy, and is predicted to be deleterious by a well characterized algorithm. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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