Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000576245 | SCV000676957 | uncertain significance | Fanconi anemia complementation group O | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 83 of the RAD51C protein (p.Lys83Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 487199). 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. 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. |
Prevention |
RCV000679798 | SCV000807168 | uncertain significance | not provided | 2017-05-26 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000679798 | SCV001770034 | uncertain significance | not provided | 2019-10-24 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002431729 | SCV002742242 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-27 | criteria provided, single submitter | clinical testing | The p.K83T variant (also known as c.248A>C), located in coding exon 2 of the RAD51C gene, results from an A to C substitution at nucleotide position 248. The lysine at codon 83 is replaced by threonine, an amino acid with similar properties. 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. |