ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.1117G>A (p.Glu373Lys)

gnomAD frequency: 0.00002  dbSNP: rs1433497291
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000705606 SCV000834611 uncertain significance Fanconi anemia complementation group O 2023-08-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 373 of the RAD51C protein (p.Glu373Lys). This variant is not present in population databases (gnomAD no frequency). 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: 581698). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 Diagnostics, LLC DBA Color Health RCV001184096 SCV001349998 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-06 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 373 of the RAD51C protein. Computational prediction tool suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold ≤0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV003227841 SCV003925045 uncertain significance not provided 2023-05-11 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 14704354)
Ambry Genetics RCV001184096 SCV004062367 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-10 criteria provided, single submitter clinical testing The p.E373K variant (also known as c.1117G>A), located in coding exon 9 of the RAD51C gene, results from a G to A substitution at nucleotide position 1117. The glutamic acid at codon 373 is replaced by lysine, an amino acid with similar properties. This amino acid position is 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.
Baylor Genetics RCV003465636 SCV004209755 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 3 2023-10-26 criteria provided, single submitter clinical testing

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