Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220155 | SCV000274507 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-23 | criteria provided, single submitter | clinical testing | The p.H233R variant (also known as c.698A>G), located in coding exon 4 of the RAD51C gene, results from an A to G substitution at nucleotide position 698. The histidine at codon 233 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly 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 variant remains unclear. |
| Invitae | RCV001046986 | SCV001210913 | uncertain significance | Fanconi anemia complementation group O | 2023-03-31 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs754895072, gnomAD 0.02%). 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 expected to disrupt RAD51C protein function. ClinVar contains an entry for this variant (Variation ID: 230833). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 233 of the RAD51C protein (p.His233Arg). |