Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001341133 | SCV001534983 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-06-17 | 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 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 been reported in individuals in the Breast Cancer Information Core database (PMID: 10923033). ClinVar contains an entry for this variant (Variation ID: 54542). This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with alanine at codon 784 of the BRCA1 protein (p.Ser784Ala). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and alanine. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001553706 | SCV001774680 | uncertain significance | not specified | 2021-07-09 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.2350T>G (p.Ser784Ala) results in a conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250640 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2350T>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002444511 | SCV002734435 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-04 | criteria provided, single submitter | clinical testing | The p.S784A variant (also known as c.2350T>G), located in coding exon 9 of the BRCA1 gene, results from a T to G substitution at nucleotide position 2350. The serine at codon 784 is replaced by alanine, an amino acid with 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, |
RCV002444511 | SCV003847735 | 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 |
RCV000111830 | SCV000144387 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2004-02-20 | no assertion criteria provided | clinical testing |