ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.727C>T (p.Arg243Cys) (rs397516265)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000629015 SCV000059648 likely pathogenic Hypertrophic cardiomyopathy 2019-02-05 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Invitae RCV000629015 SCV000749925 pathogenic Hypertrophic cardiomyopathy 2018-11-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 243 of the MYH7 protein (p.Arg243Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID:  21799269, 27247418, 27532257). ClinVar contains an entry for this variant (Variation ID: 43101). 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). A different missense substitution at this codon (p.Arg243His) has been determined to be pathogenic (PMID: 18506004, 20965760, 21551322). This suggests that the arginine residue is critical for MYH7 protein function and that other missense substitutions at this position may also be pathogenic. 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). For these reasons, this variant has been classified as Pathogenic.

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