Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000580124 | SCV000683522 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-27 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001312598 | SCV001503058 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-07-10 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 489753). 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. 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 sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1011 of the BRCA2 protein (p.Thr1011Ile). 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. |
Ambry Genetics | RCV000580124 | SCV002753441 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-13 | criteria provided, single submitter | clinical testing | The p.T1011I variant (also known as c.3032C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 3032. The threonine at codon 1011 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV000580124 | SCV003850328 | 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). |