Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000462695 | SCV000550845 | uncertain significance | Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH | 2024-02-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 265 of the BAG3 protein (p.Pro265Leu). This variant is present in population databases (rs769034041, gnomAD 0.0009%). 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: 410232). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BAG3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004022744 | SCV005021897 | uncertain significance | Cardiovascular phenotype | 2024-01-09 | criteria provided, single submitter | clinical testing | The p.P265L variant (also known as c.794C>T), located in coding exon 3 of the BAG3 gene, results from a C to T substitution at nucleotide position 794. The proline at codon 265 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Genome Diagnostics Laboratory, |
RCV001729603 | SCV001977710 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV001729603 | SCV001979575 | uncertain significance | not provided | no assertion criteria provided | clinical testing |