Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000430969 | SCV000533258 | uncertain significance | not provided | 2017-09-11 | criteria provided, single submitter | clinical testing | A novel variant of uncertain significance has been identified in the BAG3 gene. The T547P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This 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. The T547P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species. Furthermore, 2/3 in silico algorithms predict this variant likely does not alter the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. |
| Labcorp Genetics |
RCV001851067 | SCV002215626 | uncertain significance | Myofibrillar myopathy 6; Dilated cardiomyopathy 1HH | 2021-06-19 | criteria provided, single submitter | clinical testing | 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. 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 proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BAG3-related conditions. ClinVar contains an entry for this variant (Variation ID: 390435). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with proline at codon 547 of the BAG3 protein (p.Thr547Pro). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and proline. |