ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.1006A>C (p.Thr336Pro) (rs772344354)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000461973 SCV000550178 uncertain significance Fanconi anemia, complementation group O 2019-10-14 criteria provided, single submitter clinical testing This sequence change replaces threonine with proline at codon 336 of the RAD51C protein (p.Thr336Pro). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and proline. This variant is present in population databases (rs772344354, ExAC 0.01%). This variant has been reported in an individual affected with ovarian cancer (PMID: 26261251). ClinVar contains an entry for this variant (Variation ID: 409832). 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.
GeneDx RCV000477986 SCV000565461 uncertain significance not provided 2018-11-14 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.1006A>C at the cDNA level, p.Thr336Pro (T336P) at the protein level, and results in the change of a Threonine to a Proline (ACA>CCA). This variant has been observed in at least one individual with epithelial ovarian cancer (Song 2015). RAD51C Thr336Pro was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the region interaction with RAB51B, RAD51D,XRCC3 (Miller 2004). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether RAD51C Thr336Pro is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000564945 SCV000671882 uncertain significance Hereditary cancer-predisposing syndrome 2015-11-10 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000564945 SCV000691211 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-14 criteria provided, single submitter clinical testing

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