ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.135G>C (p.Glu45Asp)

dbSNP: rs371608994
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236631 SCV000293601 uncertain significance not provided 2019-05-22 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24185509)
Invitae RCV000553107 SCV000650006 uncertain significance Fanconi anemia complementation group O 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 45 of the RAD51C protein (p.Glu45Asp). This variant is present in population databases (rs371608994, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 246164). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD51C protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV000564011 SCV000667130 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-25 criteria provided, single submitter clinical testing The p.E45D variant (also known as c.135G>C), located in coding exon 1 of the RAD51C gene, results from a G to C substitution at nucleotide position 135. The glutamic acid at codon 45 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236631 SCV000889815 uncertain significance not provided 2018-01-04 criteria provided, single submitter clinical testing

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