Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588111 | SCV000699812 | uncertain significance | not provided | 2016-08-24 | criteria provided, single submitter | clinical testing | Variant summary: The c.482A>T (p.Glu161Val) in RAD51C gene is a missense change that involves a highly conserved nucleotide and 4/5 in silico tools predict damaging outcome. The variant of interest is located within a functional domain required for DNA recombination, and mutations in this region found in HBOC pts were presumably associated with RAD51C-mediated breast and ovarian cancer. The variant is absent from the control population dataset of ExAC and has not, to our knowledge, been reported in affected individuals via published reports or by reputable databases/clinical laboratories. Taking together, the variant was classified as VUS. |
Labcorp Genetics |
RCV000648259 | SCV000770073 | uncertain significance | Fanconi anemia complementation group O | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 161 of the RAD51C protein (p.Glu161Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 496504). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RAD51C protein function. 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 | RCV002331004 | SCV002634034 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-21 | criteria provided, single submitter | clinical testing | The p.E161V variant (also known as c.482A>T), located in coding exon 3 of the RAD51C gene, results from an A to T substitution at nucleotide position 482. The glutamic acid at codon 161 is replaced by valine, an amino acid with dissimilar properties. This alteration has been identified in a breast and/or ovarian cancer patient (Van Marcke C et al. Breast Cancer Res, 2020 04;22:36). 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. |
Fulgent Genetics, |
RCV005027697 | SCV005649725 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O | 2024-02-14 | criteria provided, single submitter | clinical testing |