ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1418T>C (p.Phe473Ser) (rs397515900)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158083 SCV000208018 likely pathogenic not provided 2013-01-26 criteria provided, single submitter clinical testing The Phe473Ser variant in the MYBPC3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Phe473Ser results in a non-conservative amino acid substitution of a non-polar Phenylalanine with a polar Serine at a position that is conserved across species. In silico analysis predicts Phe473Ser is probably damaging to the protein structure/function. Mutations in nearby residues (Arg470Trp, Arg470Gln, Val471Glu, Trp486Gly) have been reported in association with HCM, further supporting the functional importance of this region of the protein. Furthermore, the Phe473Ser 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.In summary, Phe473Ser is a good candidate for a disease-causing mutation. The variant is found in HCM panel(s).
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035395 SCV000059043 uncertain significance not specified 2014-06-05 criteria provided, single submitter clinical testing The Phe473Ser variant in MYBPC3 has been identified by our laboratory in 1 Cauca sian adult with HCM and was absent from large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Phe473Ser variant is uncertain.

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