Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000228849 | SCV000289772 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2015-12-07 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC, no frequency) and has not been reported in the literature. This sequence change replaces serine with arginine at codon 1042 of the BRCA1 protein (p.Ser1042Arg). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and arginine. |
Ambry Genetics | RCV002321882 | SCV002607583 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-21 | criteria provided, single submitter | clinical testing | The p.S1042R variant (also known as c.3126C>G), located in coding exon 9 of the BRCA1 gene, results from a C to G substitution at nucleotide position 3126. The serine at codon 1042 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is not 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, |
RCV002321882 | SCV003847551 | 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). |