ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4558G>A (p.Gly1520Arg) (rs763683589)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462161 SCV000546210 uncertain significance Hypertrophic cardiomyopathy 2018-09-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 1520 of the MYH7 protein (p.Gly1520Arg). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs763683589, ExAC 0.001%) but has not been reported in the literature in individuals with a MYH7-related disease. However, it has been reported in an individual with Brugada syndrome (PMID: 26220970). The clinical significance of this observation is uncertain as Brugada syndrome is not known to be associated with MYH7. 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 with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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