ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.667G>A (p.Val223Ile)

dbSNP: rs876660177
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213361 SCV000277385 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-09 criteria provided, single submitter clinical testing The p.V223I variant (also known as c.667G>A), located in coding exon 4 of the RAD51C gene, results from a G to A substitution at nucleotide position 667. The valine at codon 223 is replaced by isoleucine, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000700129 SCV000828871 uncertain significance Fanconi anemia complementation group O 2018-05-17 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 233081). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 223 of the RAD51C protein (p.Val223Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.

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