ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.779G>C (p.Arg260Pro)

dbSNP: rs730881926
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212948 SCV000211621 uncertain significance not provided 2024-04-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in an individual with a personal history of breast cancer (PMID: 25186627); This variant is associated with the following publications: (PMID: 14704354, 25186627)
Ambry Genetics RCV000160917 SCV000217529 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-27 criteria provided, single submitter clinical testing The p.R260P variant (also known as c.779G>C), located in coding exon 5 of the RAD51C gene, results from a G to C substitution at nucleotide position 779. The arginine at codon 260 is replaced by proline, an amino acid with dissimilar properties. This alteration was also detected on a 25-gene panel test in a woman of Caucasian ancestry who was diagnosed with breast cancer before age 50 (Tung N et al. Cancer, 2015 Jan;121:25-33). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000467510 SCV000550193 uncertain significance Fanconi anemia complementation group O 2024-01-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 260 of the RAD51C protein (p.Arg260Pro). This variant is present in population databases (rs730881926, 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: 182829). 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 expected to disrupt RAD51C protein function with a positive 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.
Color Diagnostics, LLC DBA Color Health RCV000160917 SCV000686389 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-06 criteria provided, single submitter clinical testing This missense variant replaces arginine with proline at codon 260 of the RAD51C protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 3/251428 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.
Baylor Genetics RCV003462103 SCV004207933 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3 2024-01-22 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212948 SCV004220153 uncertain significance not provided 2023-04-12 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000026 (3/113720 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with breast cancer (PMID: 25186627 (2015)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

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