Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000048057 | SCV000076070 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-07-06 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs80357020, gnomAD 0.005%). This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 1014 of the BRCA1 protein (p.Met1014Lys). 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 BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 54761). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. |
Ambry Genetics | RCV000129436 | SCV000184206 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-24 | criteria provided, single submitter | clinical testing | The p.M1014K variant (also known as c.3041T>A), located in coding exon 9 of the BRCA1 gene, results from a T to A substitution at nucleotide position 3041. The methionine at codon 1014 is replaced by lysine, an amino acid with 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000758805 | SCV000887656 | uncertain significance | not provided | 2022-08-03 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000129436 | SCV000909322 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-06-22 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000758805 | SCV001793112 | uncertain significance | not provided | 2019-09-03 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; Also known as BRCA1 3160T>A; This variant is associated with the following publications: (PMID: 15385441) |
Sema4, |
RCV000129436 | SCV002538177 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-23 | criteria provided, single submitter | curation | |
University of Washington Department of Laboratory Medicine, |
RCV000129436 | SCV003849168 | 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). |
Breast Cancer Information Core |
RCV000111989 | SCV000144619 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2003-12-23 | no assertion criteria provided | clinical testing | |
BRCAlab, |
RCV000111989 | SCV004244064 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-03-02 | no assertion criteria provided | clinical testing |