Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000047888 | SCV000075901 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2016-08-24 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. 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 is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BRCA1-related disease. ClinVar contains an entry for this variant (Variation ID: 54609). This sequence change replaces serine with alanine at codon 864 of the BRCA1 protein (p.Ser864Ala). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and alanine. |
| Ambry Genetics | RCV000164741 | SCV000215413 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-07-29 | criteria provided, single submitter | clinical testing | The p.S864A variant (also known as c.2590T>G or 2709T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 2590. The serine at codon 864 is replaced by alanine, an amino acid with a few similar properties. This variant was previously reported in the SNPDatabase as rs80357285. This variant was not reported in population-based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 64000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.S864A remains unclear. |
| University of Washington Department of Laboratory Medicine, |
RCV000164741 | SCV003847558 | 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). |
| Breast Cancer Information Core |
RCV000111897 | SCV000144483 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-11-25 | no assertion criteria provided | clinical testing |