ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.335G>C (p.Gly112Ala) (rs370212314)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130920 SCV000185830 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-04 criteria provided, single submitter clinical testing Insufficient or Conflicting Evidence
Invitae RCV000197831 SCV000255188 uncertain significance Fanconi anemia, complementation group O 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with alanine at codon 112 of the RAD51C protein (p.Gly112Ala). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 142093). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV000236213 SCV000293088 uncertain significance not provided 2018-04-29 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.335G>C at the cDNA level, p.Gly112Ala (G112A) at the protein level, and results in the change of a Glycine to an Alanine (GGG>GCG). This variant has been observed in an individual with a personal and/or family history of cancer (Mach?ckov? 2016). RAD51C Gly112Ala was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the region that interacts with RAD51B, RAD51D and XRCC3 and is required for Holliday junction resolution activity (Miller 2004, 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 Gly112Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000130920 SCV000686340 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-16 criteria provided, single submitter clinical testing
Mendelics RCV000709501 SCV000839325 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000236213 SCV000892227 uncertain significance not provided 2018-07-01 criteria provided, single submitter clinical testing

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