Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002394850 | SCV002703165 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-15 | criteria provided, single submitter | clinical testing | The p.C335R variant (also known as c.1003T>C), located in coding exon 8 of the RAD51C gene, results from a T to C substitution at nucleotide position 1003. The cysteine at codon 335 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |
| Labcorp Genetics |
RCV003507442 | SCV004271608 | uncertain significance | Fanconi anemia complementation group O | 2022-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 335 of the RAD51C protein (p.Cys335Arg). This variant is not present in population databases (gnomAD 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD51C protein function. ClinVar contains an entry for this variant (Variation ID: 1776439). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. |