Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001299028 | SCV001488104 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-02-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with BRCA2-related conditions. This sequence change replaces valine with leucine at codon 3240 of the BRCA2 protein (p.Val3240Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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. 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 | RCV004951460 | SCV005548718 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-03 | criteria provided, single submitter | clinical testing | The p.V3240L variant (also known as c.9718G>C), located in coding exon 26 of the BRCA2 gene, results from a G to C substitution at nucleotide position 9718. The valine at codon 3240 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |