ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.1109G>A (p.Arg370Gln) (rs373170458)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166749 SCV000217560 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-27 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000168186 SCV000218849 uncertain significance Fanconi anemia, complementation group O 2019-10-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 370 of the RAD51C protein (p.Arg370Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs373170458, ExAC 0.002%). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 187061). 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.
Color RCV000166749 SCV000691218 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-22 criteria provided, single submitter clinical testing
Counsyl RCV000662686 SCV000785405 uncertain significance Breast-ovarian cancer, familial 3; Fanconi anemia, complementation group O 2017-08-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001192875 SCV001361300 uncertain significance not specified 2019-09-13 criteria provided, single submitter clinical testing Variant summary: RAD51C c.1109G>A (p.Arg370Gln) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 248394 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1109G>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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