Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000112509 | SCV000326168 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002336193 | SCV002645244 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2018-05-15 | criteria provided, single submitter | clinical testing | The p.S1715R variant (also known as c.5145C>G), located in coding exon 16 of the BRCA1 gene, results from a C to G substitution at nucleotide position 5145. The serine at codon 1715 is replaced by arginine, an amino acid with dissimilar properties. In one study, this protein alteration segregated with disease in a Scandinavian family with hereditary breast and ovarian cancer (Vallon-Christersson J et al. Hum. Mol. Genet. 2001 Feb;10(4):353-60). Numerous functional studies have shown that this variant is functionally defective including in homology directed repair, yeast growth retardation, transcription assays, binding activity and specificity, protease sensitivity, and overall stability (Vallon-Christersson J et al. Hum. Mol. Genet. 2001 Feb;10:353-60; Anantha RW et al. Elife 2017 04;6; Thouvenot P et al. PLoS Genet. 2016 06;12:e1006096; Lee MS et al. Cancer Res. 2010 Jun;70:4880-90; Rowling PJ et al. J. Biol. Chem. 2010 Jun;285:20080-7). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Breast Cancer Information Core |
RCV000112509 | SCV000145331 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Brotman Baty Institute, |
RCV000112509 | SCV001242202 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |