ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.779G>A (p.Arg260Gln) (rs730881926)

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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 RCV000166327 SCV000217113 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000166327 SCV000686388 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780668 SCV000918127 uncertain significance not specified 2018-06-18 criteria provided, single submitter clinical testing Variant summary: RAD51C c.779G>A (p.Arg260Gln) results in a conservative amino acid change located in the DNA recombination and repair protein RecA-like, ATP-binding domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246218 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.779G>A has been reported in the literature, however this report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000529829 SCV000650024 uncertain significance Fanconi anemia, complementation group O 2018-08-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 260 of the RAD51C protein (p.Arg260Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs730881926, ExAC 0.01%). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 186692). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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