ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.5740G>A (p.Glu1914Lys) (rs397516254)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Inherited Cardiomyopathy Variant Curation Expert Panel, RCV000035983 SCV000564463 likely pathogenic Primary dilated cardiomyopathy 2016-12-15 reviewed by expert panel curation The c.5740G>A (p.Glu1914Lys) variant in MYH7 has been reported in 4 individuals with dilated cardiomyopathy, two of whom had additional myopathy features (PS4_Supporting; PMID:27532257; PMID:24664454; Partners LMM ClinVar SCV000059635.4). Additionally, in two of the probands, the variant occurred de novo (PM6; PMID:24664454). This variant was absent from large population studies (PM2; http://exac.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for dilated cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (PMID:29300372): PM2; PM6; PP3; PS4_ Supporting
GeneReviews RCV000192205 SCV000223112 pathogenic Myopathy, distal, 1 2015-03-12 no assertion criteria provided literature only
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035983 SCV000059635 pathogenic Primary dilated cardiomyopathy 2016-01-29 criteria provided, single submitter clinical testing The p.Glu1914Lys variant in MYH7 has been previously identified in 3 individuals with childhood onset of DCM and was de novo in two of them with parental relati onships confirmed (Lakdawala 2012, Lamont 2014, Pugh 2014). It was absent from l arge population studies. This variant was predicted to be pathogenic using a com putational tool clinically validated by our laboratory. This tool's pathogenic p rediction is estimated to be correct 94% of the time (Jordan 2011). In summary, this variant meets our criteria to be classified as pathogenic.
Neurogenetics Laboratory,Royal Perth Hospital RCV000132760 SCV000119911 pathogenic Dilated cardiomyopathy 1S; Myopathy, distal, 1 2013-01-01 no assertion criteria provided clinical testing

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