ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.601C>G (p.Leu201Val) (rs531838785)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000776221 SCV000911407 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586663 SCV000699817 uncertain significance not provided 2016-10-06 criteria provided, single submitter clinical testing Variant summary: The RAD51C c.601C>G (p.Leu201Val) variant causes a missense change involving a non-conserved nucleotide with 3/4 in silico tools (SNPs&GO not captured here due to low reliability index) predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 2/121042 (1/60521), which does not exceed the estimated maximal expected allele frequency for a pathogenic RAD51C variant of 1/16000. A publication cites the variant in an affected individual with a classification of "unknown significance." Reputable databases and clinical diagnositic laboratories have not, to our knowledge, cited the variant of interest. Therefore, until additional clinical and/or functional studies become available, the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)."
Invitae RCV000808711 SCV000948827 uncertain significance Fanconi anemia, complementation group O 2018-10-23 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 201 of the RAD51C protein (p.Leu201Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs531838785, ExAC 0.006%). This variant has been observed in an individual affected with breast cancer (PMID: 26976419). ClinVar contains an entry for this variant (Variation ID: 496506). 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 tolerated, 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.

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