Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000702848 | SCV000831719 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with serine at codon 636 of the BRCA1 protein (p.Cys636Ser). The cysteine residue is weakly conserved and there is a moderate physicochemical difference between cysteine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 579537). 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. 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. |
Ambry Genetics | RCV002406632 | SCV002722027 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-05-11 | criteria provided, single submitter | clinical testing | The p.C636S variant (also known as c.1907G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide position 1907. The cysteine at codon 636 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV002406632 | SCV003849647 | 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). |