Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001063663 | SCV001228520 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with isoleucine at codon 2865 of the BRCA2 protein (p.Leu2865Ile). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and isoleucine. This variant is not present in population databases (ExAC no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA2-related conditions. |
| Ambry Genetics | RCV002445330 | SCV002681323 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-07-24 | criteria provided, single submitter | clinical testing | The p.L2865I variant (also known as c.8593T>A), located in coding exon 19 of the BRCA2 gene, results from a T to A substitution at nucleotide position 8593. The leucine at codon 2865 is replaced by isoleucine, an amino acid with highly 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. |