ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.52C>T (p.Pro18Ser) (rs547142453)

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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 RCV000215646 SCV000276747 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000215646 SCV000691243 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-19 criteria provided, single submitter clinical testing
GeneDx RCV000482836 SCV000571571 uncertain significance not provided 2018-02-05 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.52C>T at the cDNA level, p.Pro18Ser (P18S) at the protein level, and results in the change of a Proline to a Serine (CCG>TCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Pro18Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). RAD51C Pro18Ser is located in the region required for holiday junction resolution activity (UniProt). In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether RAD51C Pro18Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000810573 SCV000950786 uncertain significance Fanconi anemia, complementation group O 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 18 of the RAD51C protein (p.Pro18Ser). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs547142453, ExAC 0.04%). This variant has not been reported in the literature in individuals with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 232581). 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"). 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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