Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular 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. |
| Invitae | RCV000541446 | SCV000623605 | pathogenic | Hypertrophic cardiomyopathy | 2022-11-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MYBPC3 protein in which other variant(s) (p.Arg1271*) have been determined to be pathogenic (PMID: 18533079, 23396983; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 42737). This premature translational stop signal has been observed in individuals with hypertrophic cardiomyopathy (PMID: 25611685, 26090888). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe1246Leufs*85) in the MYBPC3 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the MYBPC3 protein. |
| 3billion | RCV001807751 | SCV002059093 | pathogenic | Hypertrophic cardiomyopathy 4 | 2022-01-03 | criteria provided, single submitter | clinical testing | The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000042737, PMID:20474083). Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |