ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.121G>C (p.Val41Leu)

gnomAD frequency: 0.00003  dbSNP: rs879254131
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235241 SCV000293599 uncertain significance not provided 2022-11-11 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 reported as pathogenic or benign to our knowledge
Ambry Genetics RCV000567552 SCV000667105 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-23 criteria provided, single submitter clinical testing The p.V41L variant (also known as c.121G>C), located in coding exon 1 of the RAD51C gene, results from a G to C substitution at nucleotide position 121. The valine at codon 41 is replaced by leucine, an amino acid with highly 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.
Invitae RCV000648254 SCV000770068 uncertain significance Fanconi anemia complementation group O 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 41 of the RAD51C protein (p.Val41Leu). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 246163). 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.
Fulgent Genetics, Fulgent Genetics RCV002500834 SCV002778937 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O 2021-12-03 criteria provided, single submitter clinical testing

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