ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.883C>G (p.Leu295Val) (rs752910287)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476276 SCV000551362 uncertain significance Breast-ovarian cancer, familial 4 2019-11-08 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 295 of the RAD51D protein (p.Leu295Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs752910287, ExAC 0.002%). This variant has not been reported in the literature in individuals with a RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 410562). 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, this variant has uncertain impact on RAD51D function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000484734 SCV000567475 uncertain significance not provided 2018-03-06 criteria provided, single submitter clinical testing This variant is denoted RAD51D c.883C>G at the cDNA level, p.Leu295Val (L295V) at the protein level, and results in the change of a Leucine to a Valine (CTG>GTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51D Leu295Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). RAD51D Leu295Val is located in the ATPase domain (Miller 2004). In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available information, it is unclear whether RAD51D Leu295Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000561823 SCV000663815 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-17 criteria provided, single submitter clinical testing Insufficient evidence
Color RCV000561823 SCV000904084 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-03 criteria provided, single submitter clinical testing

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