ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.1220G>T (p.Gly407Val) (rs397516095)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000465369 SCV000546216 likely pathogenic Hypertrophic cardiomyopathy 2017-06-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 407 of the MYH7 protein (p.Gly407Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in an individual affected with hypertrophic cardiomyopathy (HCM) (PMID: 15358028). ClinVar contains an entry for this variant (Variation ID: 42831). 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, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000465369 SCV000059360 likely pathogenic Hypertrophic cardiomyopathy 2018-04-06 criteria provided, single submitter clinical testing The p.Gly407Val variant in MYH7 has been identified in 2 individuals with HCM (V an Driest 2004, LMM data) and was absent from large population studies. This var iant has also been reported in ClinVar (Variation ID #42831). Computational pred iction tools and conservation analysis suggest that the p.Gly407Val variant may impact the protein, though this information is not predictive enough to determin e pathogenicity. Of note, this variant lies in the head region of the protein. M issense variants in this region have been reported and statistically indicated t o be more likely to cause disease (Walsh 2016). In summary, although additional studies are required to fully establish its clinical significance, the p.Gly407V al variant is likely pathogenic. ACMG/AMP Criteria applied: PM1; PM2; PP3; PS4_S upporting.

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