ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.721G>A (p.Val241Met) (rs886039000)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484993 SCV000565271 uncertain significance not provided 2018-10-29 criteria provided, single submitter clinical testing The V241M variant has not been published as a pathogenic variant or been reported as a benign polymorphism to our knowledge. The V241M variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the V241M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties; it is located in the Ig-like C2-type 1 functional domain of the MYBPC3 gene. This substitution occurs at a position that is well conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (Y237H, Y237C, Y237S, R238H, E240D, S242P) have been reported in Human Gene Mutation Database in association with cardiomyopathy (Stenson P et al., 2014), supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Ambry Genetics RCV000622157 SCV000740152 uncertain significance Cardiovascular phenotype 2017-05-15 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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