Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000695758 | SCV000824276 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-05-22 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 573951). 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. This variant disrupts the p.Leu3101 amino acid residue in BRCA2. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae; external communication). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function. This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 3101 of the BRCA2 protein (p.Leu3101Gln). |
| Ambry Genetics | RCV002369890 | SCV002686900 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-09-14 | criteria provided, single submitter | clinical testing | The p.L3101Q variant (also known as c.9302T>A), located in coding exon 24 of the BRCA2 gene, results from a T to A substitution at nucleotide position 9302. The leucine at codon 3101 is replaced by glutamine, an amino acid with dissimilar properties. This variant was identified in 1/882 Chinese individuals who underwent multi-gene panel testing for HBOC risk assessment (Shao D et al. Cancer Sci, 2020 Feb;111:647-657). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |