Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000804687 | SCV000944607 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-07-26 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA2-related disease. This sequence change replaces glycine with valine at codon 561 of the BRCA2 protein (p.Gly561Val). The glycine residue is moderately conserved and there is a moderate physicochemical difference between glycine and valine. |
Ambry Genetics | RCV002397634 | SCV002711013 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-18 | criteria provided, single submitter | clinical testing | The p.G561V variant (also known as c.1682G>T), located in coding exon 9 of the BRCA2 gene, results from a G to T substitution at nucleotide position 1682. The glycine at codon 561 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not well 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, |
RCV002397634 | SCV003851572 | 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). |