ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.492T>G (p.Phe164Leu) (rs573992101)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000446053 SCV000663768 uncertain significance Hereditary cancer-predisposing syndrome 2016-05-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000446053 SCV000537571 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-19 criteria provided, single submitter clinical testing
Counsyl RCV000168314 SCV000490089 uncertain significance Fanconi anemia, complementation group O 2016-11-02 criteria provided, single submitter clinical testing
Counsyl RCV000408982 SCV000490090 uncertain significance Breast-ovarian cancer, familial 3 2016-11-02 criteria provided, single submitter clinical testing
GeneDx RCV000656962 SCV000292676 uncertain significance not provided 2018-04-06 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.492T>G at the cDNA level, p.Phe164Leu (F164L) at the protein level, and results in the change of a Phenylalanine to a Leucine (TTT>TTG). This variant was observed in at least two patients meeting criteria for hereditary breast and ovarian cancer testing, one also harboring a co-occurring pathogenic variant in BRCA1 (Cock-Rada 2017). RAD51C Phe164Leu was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the region of interaction with RAD51B, 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 Phe164Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000168314 SCV000218998 uncertain significance Fanconi anemia, complementation group O 2019-01-04 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 164 of the RAD51C protein (p.Phe164Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs573992101, ExAC 0.03%). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 188317). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000235901 SCV000602140 uncertain significance not specified 2017-04-27 criteria provided, single submitter clinical testing

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