Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000580008 | SCV000683227 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-01 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with methionine at codon 1645 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). This variant has been reported to be partially functional in a haploid cell proliferation assay (PMID: 30209399). This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Labcorp Genetics |
RCV002513662 | SCV003496322 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-03-20 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 1645 of the BRCA1 protein (p.Arg1645Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 55320). 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 BRCA1 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. |
| Breast Cancer Information Core |
RCV000112425 | SCV000145212 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 1999-06-22 | no assertion criteria provided | clinical testing | |
| Brotman Baty Institute, |
RCV000112425 | SCV001243236 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |