ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2849C>T (p.Ala950Val) (rs730880577)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158190 SCV000208125 uncertain significance not provided 2017-02-03 criteria provided, single submitter clinical testing This variant is dentoed p.Ala950Val (GCA>GTA): c.2849 C>T in exon 27 of the MYBPC3 gene (NM_000256.3). The A950V variant in the MYBPC3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The A950V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts A950V is probably damaging to the protein structure/function. Splice algorithms also predict A950V may affect splicing, creating a cryptic splice donor site. Mutations in nearby residues (R943Q, T957S, T958I) have been reported in association with HCM, further supporting the functional importance of this region of the protein. Furthermore, the A950V variant was not observed in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in HCM panel(s).
Ambry Genetics RCV000619159 SCV000735856 uncertain significance Cardiovascular phenotype 2017-04-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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