Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131650 | SCV000186677 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-04 | criteria provided, single submitter | clinical testing | The p.A279P variant (also known as c.835G>C), located in coding exon 5 of the RAD51C gene, results from a G to C substitution at nucleotide position 835. The alanine at codon 279 is replaced by proline, an amino acid with highly similar properties. This variant was previously detected in 1/1404 affected cases from ovarian cancer families and in 0/1156 healthy controls (Loveday C et al. Nat. Genet. 2012 Apr;44(5):475-6). In another study, this variant was seen in 1/3429 patients with invasive epithelial ovarian cancer and 0/2722 controls (Song H et al. J. Clin. Oncol., 2015 Sep;33(26):2901-7). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000168079 | SCV000218733 | uncertain significance | Fanconi anemia complementation group O | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 279 of the RAD51C protein (p.Ala279Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 22538716, 26261251). ClinVar contains an entry for this variant (Variation ID: 142502). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Color Diagnostics, |
RCV000131650 | SCV000686394 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-02-24 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003422028 | SCV004117581 | uncertain significance | RAD51C-related condition | 2023-07-20 | criteria provided, single submitter | clinical testing | The RAD51C c.835G>C variant is predicted to result in the amino acid substitution p.Ala279Pro. This variant has been reported in an individual with breast and/or ovarian cancer (Table S3, Loveday et al. 2012. PubMed ID: 22538716; Table A4, Song et al. 2015. PubMed ID: 26261251; Table 1, Gayarre et al. 2017. PubMed ID: 28829762; Table S1, Boni et al. 2021. PubMed ID: 34923718). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/142502/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Baylor Genetics | RCV003467178 | SCV004207944 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-09-09 | criteria provided, single submitter | clinical testing |