Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001242441 | SCV001415528 | uncertain significance | Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 510 of the BAG3 protein (p.Leu510Phe). This variant is present in population databases (rs771188059, gnomAD 0.01%). 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: 967509). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | RCV002393627 | SCV002705178 | uncertain significance | Cardiovascular phenotype | 2020-12-28 | criteria provided, single submitter | clinical testing | The p.L510F variant (also known as c.1528C>T), located in coding exon 4 of the BAG3 gene, results from a C to T substitution at nucleotide position 1528. The leucine at codon 510 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |