ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.71G>A (p.Arg24Gln) (rs777554369)

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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 RCV000220751 SCV000272990 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-01 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000590703 SCV000567204 uncertain significance not provided 2017-02-23 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.71G>A at the cDNA level, p.Arg24Gln (R24Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGG>CAG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Arg24Gln was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Glutamine differ in some properties, this is considered a semi-conservative amino acid substitution. RAD51C Arg24Gln occurs at a position that is not conserved and is located within the region required for Holliday junction resolution activity (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether RAD51C Arg24Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000529013 SCV000660415 uncertain significance Fanconi anemia, complementation group O 2019-07-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 24 of the RAD51C protein (p.Arg24Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs777554369, 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: 229691). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or 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.
Color RCV000220751 SCV000691264 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590703 SCV000699819 uncertain significance not provided 2016-02-23 criteria provided, single submitter clinical testing

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