Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001975373 | SCV002249974 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-06-28 | 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. 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 with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 2393 of the BRCA2 protein (p.Met2393Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. |
| Ambry Genetics | RCV004946947 | SCV005551880 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-25 | criteria provided, single submitter | clinical testing | The p.M2393I variant (also known as c.7179G>T), located in coding exon 13 of the BRCA2 gene, results from a G to T substitution at nucleotide position 7179. The methionine at codon 2393 is replaced by isoleucine, 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. |