Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000648223 | SCV000770037 | uncertain significance | Fanconi anemia complementation group O | 2022-08-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 538763). This variant is present in population databases (rs779932777, gnomAD 0.0009%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 190 of the RAD51C protein (p.Glu190Lys). |
Color Diagnostics, |
RCV003584694 | SCV004357116 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 190 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. In an international breast cancer case-control meta-analysis, this variant was detected in 1/60466 cases and absent in 53461 unaffected controls (PMID: 33471991). This variant has been identified in 1/251456 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |