Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000689668 | SCV000817331 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2020-04-03 | 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. 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"). This variant has not been reported in the literature in individuals with BRCA1-related disease, but has been reported in an unaffected control (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 569120). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with isoleucine at codon 782 of the BRCA1 protein (p.Ser782Ile). The serine residue is moderately conserved and there is a large physicochemical difference between serine and isoleucine. |
| Ambry Genetics | RCV001015243 | SCV001176058 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-17 | criteria provided, single submitter | clinical testing | The p.S782I variant (also known as c.2345G>T), located in coding exon 9 of the BRCA1 gene, results from a G to T substitution at nucleotide position 2345. The serine at codon 782 is replaced by isoleucine, an amino acid with dissimilar properties. In one study, this alteration was not detected in 53 unselected male breast cancer patients but was detected in 1/12490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun. 2018 Oct;9:4083). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| University of Washington Department of Laboratory Medicine, |
RCV001015243 | SCV003847739 | 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). |