Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000215570 | SCV000271206 | likely pathogenic | Primary dilated cardiomyopathy | 2017-04-07 | criteria provided, single submitter | clinical testing | The p.Gln244X variant in BAG3 has been identified by our laboratory in 1 individ ual with DCM and segregated with disease in 2 affected relatives (including 1 ob ligate carrier; LMM data). It was also absent from large population studies. Thi s variant has been reported in ClinVar (Variation ID 228246). This nonsense vari ant leads to a premature termination codon at position 244, which is predicted t o lead to a truncated or absent protein. Nonsense and other truncating variants in BAG3 are associated with DCM (Norton 2011, Villard 2011, Konersman 2015). In summary, although additional studies are required to fully establish its clinica l significance, the p.Gln244X variant is likely pathogenic. |
| Invitae | RCV000689286 | SCV000816928 | pathogenic | Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln244*) in the BAG3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BAG3 are known to be pathogenic (PMID: 21353195, 25008357). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BAG3-related conditions. ClinVar contains an entry for this variant (Variation ID: 228246). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV003327382 | SCV004034706 | likely pathogenic | not provided | 2023-09-05 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease |