ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.34C>T (p.Arg12Trp) (rs28910276)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000574346 SCV000671901 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000574346 SCV000686345 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-22 criteria provided, single submitter clinical testing
GeneDx RCV000485483 SCV000567112 uncertain significance not provided 2018-03-23 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.34C>T at the cDNA level, p.Arg12Trp (R12W) at the protein level, and results in the change of an Arginine to a Tryptophan (CGG>TGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Arg12Trp was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the region required for Holliday junction resolution activity (Uniprot). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether RAD51C Arg12Trp is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000464422 SCV000550187 uncertain significance Fanconi anemia, complementation group O 2018-12-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 12 of the RAD51C protein (p.Arg12Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs28910276, ExAC 0.002%). This variant has been reported in the literature in an individual with breast cancer (PMID: 21537932). ClinVar contains an entry for this variant (Variation ID: 409837). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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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