Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000047707 | SCV000075720 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-09-26 | criteria provided, single submitter | clinical testing | 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: 54457). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 696 of the BRCA1 protein (p.Thr696Ala). |
| Ambry Genetics | RCV000562283 | SCV000665850 | likely benign | Hereditary cancer-predisposing syndrome | 2016-06-02 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| University of Washington Department of Laboratory Medicine, |
RCV000562283 | SCV003849513 | 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). |
| Gene |
RCV003319315 | SCV004023612 | uncertain significance | not provided | 2023-02-01 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 2205A>G; This variant is associated with the following publications: (PMID: 29884841, 12872263, 32377563, 15343273) |
| Breast Cancer Information Core |
RCV000111767 | SCV000144298 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2003-12-23 | no assertion criteria provided | clinical testing |