ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.709T>C (p.Tyr237His) (rs730880624)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621974 SCV000740026 uncertain significance Cardiovascular phenotype 2016-09-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
CeGaT Praxis fuer Humangenetik Tuebingen RCV000158306 SCV000574883 uncertain significance not provided 2016-11-30 criteria provided, single submitter clinical testing
GeneDx RCV000158306 SCV000208241 likely pathogenic not provided 2017-10-06 criteria provided, single submitter clinical testing The Y237H likely pathogenic variant in the MYBPC3 gene has been reported previously in oneindividual diagnosed with HCM (Waldmuller et al., 2008). Y237H has been identified independently ofadditional cardiogenetic variants in several other individuals referred for HCM genetic testing atGeneDx. However, thus far, segregation data is limited or absent due to the lack of clinical informationprovided and/or insufficient participation by informative family members.The Y237H variant is not observed in large population cohorts (Lek et al., 2016). Furthermore, theY237H variant is a non-conservative amino acid substitution, which is likely to impact secondaryprotein structure as these residues differ in polarity, charge, size and/or other properties. In addition,this substitution occurs at a position that is conserved across species, and in silico analysis predicts thisvariant is probably damaging to the protein structure/function. Lastly, missense variants in this residue(Y237C, Y237S) have been reported in the Human Gene Mutation Database in association withcardiomyopathy (Stenson et al., 2014), supporting the functional importance of this residue and thisregion of the protein.

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