ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.200A>G (p.Glu67Gly) (rs375451955)

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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 RCV000160920 SCV000215378 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000160920 SCV000686332 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-03 criteria provided, single submitter clinical testing
GeneDx RCV000212936 SCV000211624 uncertain significance not provided 2018-06-14 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.200A>G at the cDNA level, p.Glu67Gly (E67G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAA>GGA). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. RAD51C Glu67Gly 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 that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether RAD51C Glu67Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000227460 SCV000291215 uncertain significance Fanconi anemia, complementation group O 2018-12-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glycine at codon 67 of the RAD51C protein (p.Glu67Gly). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is present in population databases (rs375451955, ExAC 0.06%). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 182832). 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: "Benign"; Align-GVGD: "Class C0"). 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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