ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.736C>T (p.Arg246Cys) (rs794729194)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000184006 SCV000236500 uncertain significance not provided 2014-09-02 criteria provided, single submitter clinical testing p.Arg246Cys (CGT>TGT): c.736 C>T in exon 6 of the VCL gene (NM_014000.2). Although rare, mutations in the VCL gene have been reported in association with DCM (Maeda M et al., 1997; Olson T et al., 2002). A variant of unknown significance has been identified in the VCL gene. The R246C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R246C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R246C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have not been reported, indicating this region of the protein may tolerate change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).

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