ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.1934C>T (p.Pro645Leu) (rs397515938)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208032 SCV000264031 likely pathogenic Primary familial hypertrophic cardiomyopathy 2015-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000158134 SCV000208069 likely pathogenic not provided 2014-05-12 criteria provided, single submitter clinical testing p.Pro645Leu (CCC>CTC): c.1934 C>T in exon 21 of the MYBPC3 gene (NM_000256.3) The P645L variant that is likely pathogenic was identified in the MYBPC3 gene. It has not been published as a mutation or reported as a benign polymorphism to our knowledge. The P645L 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. The P645L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (R654C, R654H) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein.Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. Mutations in the MYBPC3 gene have been reported in 20%-30% of patients with autosomal dominant familial hypertrophic cardiomyopathy, and have been reported less frequently in patients with autosomal dominant familial dilated cardiomyopathy (Cirino A et al., 2011; Hershberger R et al., 2009). The variant is found in HCM panel(s).
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000035454 SCV000059102 uncertain significance not specified 2018-01-05 criteria provided, single submitter clinical testing The p.Pro645Leu variant in MYBPC3 has been identified by our laboratory in 2 ind ividuals with HCM, one of whom also carried a likely pathogenic variant in MYBPC 3. It was absent from large population studies. This variant has been reported i n ClinVar (Variation ID: 42586). Computational prediction tools and conservation analysis suggest that the p.Pro645Leu variant may impact the protein, though th is information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Pro645Leu variant is uncertain.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000035454 SCV000748015 uncertain significance not specified 2016-06-14 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.