Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000215034 | SCV000276790 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-14 | criteria provided, single submitter | clinical testing | The p.D318H variant (also known as c.952G>C), located in coding exon 7 of the RAD51C gene, results from a G to C substitution at nucleotide position 952. The aspartic acid at codon 318 is replaced by histidine, an amino acid with similar properties. This amino acid position is 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. |
| Invitae | RCV000457566 | SCV000550203 | uncertain significance | Fanconi anemia complementation group O | 2023-08-05 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 318 of the RAD51C protein (p.Asp318His). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. 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: 232615). |