Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001901244 | SCV002160873 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-01-11 | 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. Experimental studies have shown that this variant does not affect mRNA splicing (PMID: 18273839). 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. This variant has not been reported in the literature in individuals with BRCA1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 690 of the BRCA1 protein (p.Lys690Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. |
| University of Washington Department of Laboratory Medicine, |
RCV003156820 | SCV003849528 | 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). |
| MGZ Medical Genetics Center | RCV003607429 | SCV004543929 | likely benign | Familial cancer of breast | 2024-02-09 | criteria provided, single submitter | clinical testing | ACMG codes applied following ENIGMA VCEP rules: BP1_STR, PM2_SUP |