Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000158368 | SCV000208303 | likely pathogenic | not provided | 2016-10-07 | criteria provided, single submitter | clinical testing | Although the c.2532_2538delGCGCGTC likely pathogenic variant in the MYBPC3 gene has not been reported to our knowledge, it has been identified in conjunction with additional cardiogenetic variants in one other individual referred for cardiomyopathy genetic testing at GeneDx. However, observation in this individual, for whom segregation data is lacking, is not sufficient to determine the absolute pathogenicity of this variant. This variant causes a shift in reading frame starting at codon Methionine 844, changing it to an Isoleucine, and creating a premature stop codon at position 33 of the new reading frame, denoted p.Met844IlefsX33. This likely pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift variants in the MYBPC3 gene, including several downstream, have been reported in the Human Gene Mutation Database in association with cardiomyopathy (Stenson et al., 2014). Furthermore, the c.2532_2538delGCGCGTC variant was not observed in approximately 6,500 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, c.2532_2538delGCGCGTC in the MYBPC3 gene is expected to be pathogenic. |
| Labcorp Genetics |
RCV001061018 | SCV001225742 | pathogenic | Hypertrophic cardiomyopathy | 2019-04-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Met844Ilefs*33) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 181081). Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). For these reasons, this variant has been classified as Pathogenic. |
| CHEO Genetics Diagnostic Laboratory, |
RCV001798535 | SCV002042169 | likely pathogenic | Cardiomyopathy | 2022-10-18 | criteria provided, single submitter | clinical testing |