Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000205015 | SCV000259955 | uncertain significance | Fanconi anemia complementation group O | 2024-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 174 of the RAD51C protein (p.Thr174Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29522266). ClinVar contains an entry for this variant (Variation ID: 219853). 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 not expected to disrupt RAD51C protein function with a negative 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. |
| Gene |
RCV000486898 | SCV000567745 | uncertain significance | not provided | 2023-08-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer (Hauke et al., 2018); This variant is associated with the following publications: (PMID: 14704354, 29522266) |
| Ambry Genetics | RCV000570805 | SCV000671923 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-07 | criteria provided, single submitter | clinical testing | The p.T174A variant (also known as c.520A>G), located in coding exon 3 of the RAD51C gene, results from an A to G substitution at nucleotide position 520. The threonine at codon 174 is replaced by alanine, an amino acid with similar properties. This alteration was detected in 1/5589 German BRCA1/2-negative probands with breast cancer (Hauke J et al. Cancer Med. 2018 04;7:1349-1358). 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. |
| Counsyl | RCV000663210 | SCV000786394 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O | 2018-04-24 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000486898 | SCV002046606 | uncertain significance | not provided | 2021-01-22 | criteria provided, single submitter | clinical testing | |
| Myriad Genetics, |
RCV003316135 | SCV004019928 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-04-05 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
| Baylor Genetics | RCV003316135 | SCV005053980 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-11-21 | criteria provided, single submitter | clinical testing |