Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000806832 | SCV000946851 | pathogenic | Hypertrophic cardiomyopathy | 2023-03-30 | 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, 19574547, 19996403, 23396983, 27532257). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 651464). This frameshift has been observed in individual(s) with clinical features of MYBPC3-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change results in a frameshift in the MYBPC3 gene (p.Arg1267Alafs*64). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 8 amino acid(s) of the MYBPC3 protein and extend the protein by 55 additional amino acid residues. |
3billion | RCV002283513 | SCV002573179 | pathogenic | Hypertrophic cardiomyopathy 4 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. It is predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with MYBPC3-related disorder (ClinVar ID: VCV000651464). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |