Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000217976 | SCV000278408 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-23 | criteria provided, single submitter | clinical testing | The p.Q133K variant (also known as c.397C>A), located in coding exon 2 of the RAD51C gene, results from a C to A substitution at nucleotide position 397. The glutamine at codon 133 is replaced by lysine, an amino acid with similar properties. This variant has been identified in breast and ovarian cancer cohorts (Song H et al. J Clin Oncol, 2015 Sep;33:2901-7; Hauke J et al. Cancer Med, 2018 04;7:1349-1358). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000236579 | SCV000293947 | uncertain significance | not provided | 2018-07-02 | criteria provided, single submitter | clinical testing | This variant is denoted RAD51C c.397C>A at the cDNA level, p.Gln133Lys (Q133K) at the protein level, and results in the change of a Glutamine to a Lysine (CAA>AAA). This variant has been identified in at least one individual with ovarian cancer and in one individual with breast cancer (Cunningham 2014, Song 2015, Hauke 2018). RAD51C Gln133Lys was not observed in large population cohorts (Lek 2016). This variant is located in the region of interaction with RAD51B, RAD51D and XRCC3 (Miller 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether RAD51C Gln133Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV000648257 | SCV000770071 | uncertain significance | Fanconi anemia complementation group O | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 133 of the RAD51C protein (p.Gln133Lys). 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: 233936). 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 with a positive predictive value of 80%. 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. |
| Baylor Genetics | RCV003469089 | SCV004208010 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-05-09 | criteria provided, single submitter | clinical testing |