ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3735del (p.Phe1246fs) (rs397516038)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541446 SCV000623605 pathogenic Hypertrophic cardiomyopathy 2017-08-07 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the MYBPC3 gene (p.Phe1246Leufs*85). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acids of the MYBPC3 protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in two individuals affected with hypertrophic cardiomyopathy (PMID: 25611685, 26090888). ClinVar contains an entry for this variant (Variation ID: 42737). A different truncation downstream of this variant (p.Arg1271*) has been determined to be pathogenic (PMID: 18533079, 23396983, Invitae). This suggests that deletion of this region of the MYBPC3 protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000541446 SCV000059263 likely pathogenic Hypertrophic cardiomyopathy 2018-01-31 criteria provided, single submitter clinical testing The p.Phe1246LeufsExtX55 variant in MYBPC3 has been identified in 2 individuals with HCM and segregated with disease in 2 affected relatives from one family (Li u 2016, LMM data). It was absent from large population studies. This variant is predicted to cause a frameshift altering the protein?s terminal 30 amino acid se quence beginning at position 1246, abolishing the stop codon and extending the p rotein by 55 amino acids. In summary, although additional studies are required t o fully establish its clinical significance, the p.Phe1246LeufsExtX55 variant is likely pathogenic. ACMG/AMP Criteria applied: PM4_S; PM2, PS4_P.

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.