Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000167983 | SCV000218631 | uncertain significance | Fanconi anemia complementation group O | 2023-11-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 40 of the RAD51C protein (p.Glu40Lys). 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: 188123). 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 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. |
| Ambry Genetics | RCV000220378 | SCV000276508 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-08 | criteria provided, single submitter | clinical testing | The p.E40K variant (also known as c.118G>A), located in coding exon 1 of the RAD51C gene, results from a G to A substitution at nucleotide position 118. The glutamic acid at codon 40 is replaced by lysine, an amino acid with similar properties. This amino acid position is 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. |
| Gene |
RCV000482450 | SCV000568001 | uncertain significance | not provided | 2023-05-30 | 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; Has not been previously published as pathogenic or benign to our knowledge |
| Color Diagnostics, |
RCV000220378 | SCV000909436 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-29 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000482450 | SCV001134783 | uncertain significance | not provided | 2018-11-01 | criteria provided, single submitter | clinical testing | |
| Center for Genomics, |
RCV002053996 | SCV002495911 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O | 2021-07-09 | criteria provided, single submitter | clinical testing | RAD51C NM_058216.1 exon 1 p.Glu40Lys (c.118G>A): This variant has not been reported in the literature and is not present in large control databases. This variant is present in ClinVar (Variation ID:188123). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
| Fulgent Genetics, |
RCV002053996 | SCV002789939 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O | 2022-05-24 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003462254 | SCV004207948 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-09-06 | criteria provided, single submitter | clinical testing |