Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000637557 | SCV000759021 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2017-09-17 | 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 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with arginine at codon 855 of the BRCA1 protein (p.Gln855Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. |
Ambry Genetics | RCV002424405 | SCV002740240 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-18 | criteria provided, single submitter | clinical testing | The p.Q855R variant (also known as c.2564A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 2564. The glutamine at codon 855 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly 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, |
RCV002424405 | SCV003847573 | 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). |