Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025952 | SCV001188241 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-18 | criteria provided, single submitter | clinical testing | The p.I2344M variant (also known as c.7032A>G), located in coding exon 13 of the BRCA2 gene, results from an A to G substitution at nucleotide position 7032. The isoleucine at codon 2344 is replaced by methionine, 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. |
Color Diagnostics, |
RCV001025952 | SCV001355540 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV003645154 | SCV004447459 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-08-16 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2344 of the BRCA2 protein (p.Ile2344Met). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. 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. ClinVar contains an entry for this variant (Variation ID: 826788). |