Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000648226 | SCV000770040 | uncertain significance | Fanconi anemia complementation group O | 2020-07-26 | criteria provided, single submitter | clinical testing | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 538766). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with arginine at codon 82 of the RAD51C protein (p.His82Arg). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and arginine. |
Color Diagnostics, |
RCV001191945 | SCV001359886 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-22 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with arginine at codon 82 of the RAD51C protein. Computational prediction tools and conservation analyses suggest that this variant may not impact protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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. |
Ambry Genetics | RCV001191945 | SCV002738191 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-21 | criteria provided, single submitter | clinical testing | The p.H82R variant (also known as c.245A>G), located in coding exon 2 of the RAD51C gene, results from an A to G substitution at nucleotide position 245. The histidine at codon 82 is replaced by arginine, an amino acid with highly similar properties. This variant was observed in an individual who was diagnosed with breast cancer at age 29 (Lerner-Ellis J et al. J Cancer Res Clin Oncol. 2021 147, 871–879). 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. |
Baylor Genetics | RCV003465410 | SCV004207954 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-08-31 | criteria provided, single submitter | clinical testing |