Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000637627 | SCV000759093 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-09-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with cysteine at codon 819 of the BRCA1 protein (p.Ser819Cys). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and cysteine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 156187). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is present in population databases (rs192655097, ExAC 0.01%). |
| Ambry Genetics | RCV002444597 | SCV002732217 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-02 | criteria provided, single submitter | clinical testing | The p.S819C variant (also known as c.2456C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 2456. The serine at codon 819 is replaced by cysteine, an amino acid with dissimilar 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. |
| University of Washington Department of Laboratory Medicine, |
RCV002444597 | SCV003847656 | 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). |
| Sharing Clinical Reports Project |
RCV000144204 | SCV000189277 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2010-12-03 | no assertion criteria provided | clinical testing |