ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1193G>A (p.Gly398Glu) (rs730880158)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000157354 SCV000207092 uncertain significance Cardiomyopathy 2014-10-28 no assertion criteria provided clinical testing
Invitae RCV000537983 SCV000623636 likely pathogenic Hypertrophic cardiomyopathy 2017-05-07 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 398 of the MYH7 protein (p.Gly398Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (rs730880158, ExAC no frequency). This variant has been reported in multiple unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 18533079, 27247418, Invitae). ClinVar contains an entry for this variant (Variation ID: 180434). 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 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 has been observed in several affected individuals and is found in an important region of the MYH7 gene. However, a gene-specific algorithm has predicted this missense change to be tolerated. In the absence of functional or segregation data, at this time this variant has been classified as Likely Pathogenic.

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