Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001205615 | SCV001376882 | uncertain significance | Fanconi anemia complementation group O | 2024-11-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 189 of the RAD51C protein (p.Gly189Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26261251). ClinVar contains an entry for this variant (Variation ID: 936752). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt RAD51C protein function with a positive predictive value of 95%. 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. |
Ambry Genetics | RCV002348672 | SCV002652377 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-22 | criteria provided, single submitter | clinical testing | The p.G189R variant (also known as c.565G>A), located in coding exon 3 of the RAD51C gene, results from a G to A substitution at nucleotide position 565. The glycine at codon 189 is replaced by arginine, an amino acid with dissimilar properties. This alteration was identified in an individual diagnosed with ovarian cancer (Song H et al. J. Clin. Oncol., 2015 Sep;33:2901-7). This amino acid position is not 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. |