Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000228353 | SCV000291241 | uncertain significance | Fanconi anemia complementation group O | 2015-11-13 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This sequence change replaces arginine with tryptophan at codon 24 of the RAD51C protein (p.Arg24Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature. |
| Ambry Genetics | RCV003298307 | SCV004000904 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-17 | criteria provided, single submitter | clinical testing | The p.R24W variant (also known as c.70C>T), located in coding exon 1 of the RAD51C gene, results from a C to T substitution at nucleotide position 70. The arginine at codon 24 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration was observed in a 30 year old Chinese woman with breast cancer; functional testing indicated mild sensitivity to MMC, etoposide and PARP inhibition (Kolinjivadi AM et al. Hum Mol Genet, 2023 Apr;32:1401-1409). 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. |