ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.773G>C (p.Arg258Pro)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000799964 SCV000939658 uncertain significance Fanconi anemia, complementation group O 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 258 of the RAD51C protein (p.Arg258Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD51C-related disease. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Variants that disrupt the p.Arg258 amino acid residue in RAD51C have been observed in affected individuals (PMID: 20400963, 25154786, 26740214). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. 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.

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