Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001343730 | SCV001537736 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1140 of the BRCA2 protein (p.Ser1140Thr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 51459). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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. |
| Ambry Genetics | RCV002453347 | SCV002617905 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-10 | criteria provided, single submitter | clinical testing | The p.S1140T variant (also known as c.3419G>C), located in coding exon 10 of the BRCA2 gene, results from a G to C substitution at nucleotide position 3419. The serine at codon 1140 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly 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. |
| University of Washington Department of Laboratory Medicine, |
RCV002453347 | SCV003851947 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003476923 | SCV004219589 | uncertain significance | not provided | 2023-01-27 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.0000087 (1/114586 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with breast cancer in a breast cancer association study (PMID: 33471991 (2021)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Breast Cancer Information Core |
RCV000113174 | SCV000146229 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 1999-04-05 | no assertion criteria provided | clinical testing |