Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000544921 | SCV000635308 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-10-19 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA2-related disease. This sequence change replaces glutamine with glutamic acid at codon 126 of the BRCA2 protein (p.Gln126Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. |
| Ambry Genetics | RCV002367819 | SCV002625970 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-27 | criteria provided, single submitter | clinical testing | The p.Q126E variant (also known as c.376C>G), located in coding exon 3 of the BRCA2 gene, results from a C to G substitution at nucleotide position 376. The glutamine at codon 126 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is not well 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. |