Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573436 | SCV000664922 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-11 | criteria provided, single submitter | clinical testing | The p.G264V variant (also known as c.791G>T), located in coding exon 5 of the RAD51C gene, results from a G to T substitution at nucleotide position 791. The glycine at codon 264 is replaced by valine, an amino acid with dissimilar properties. In a study of 1100 German high-risk breast and/or ovarian cancer families, this alteration was detected in 1 breast cancer family and produced functional study results similar to wild type RAD51C (Meindl A et al. Nat. Genet., 2010 May;42:410-4). 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. |
| Invitae | RCV000648255 | SCV000770069 | uncertain significance | Fanconi anemia complementation group O | 2021-01-15 | criteria provided, single submitter | clinical testing | An experimental study using RAD51C-deficient cell lines showed that RAD51C protein containing this missense change rescued mitomicyin C hypersensitivity and normal RAD51 foci formation after DNA damage to levels comparable to those of the wild-type protein (PMID: 20400964). This variant has been reported in an individual affected with breast cancer (PMID: 20400964). ClinVar contains an entry for this variant (Variation ID: 480946). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with valine at codon 264 of the RAD51C protein (p.Gly264Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. 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. |
| Leiden Open Variation Database | RCV001195026 | SCV001365278 | likely benign | not specified | 2014-11-02 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Johan den Dunnen. |