ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.960G>C (p.Lys320Asn) (rs864622395)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213392 SCV000276618 uncertain significance Hereditary cancer-predisposing syndrome 2015-06-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign)
Integrated Genetics/Laboratory Corporation of America RCV000780666 SCV000918125 uncertain significance not specified 2018-10-19 criteria provided, single submitter clinical testing Variant summary: RAD51C c.960G>C (p.Lys320Asn) results in a non-conservative amino acid change located in the DNA recombination and repair protein Rad51-like, C-terminal domain (IPR013632) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 246074 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.960G>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000204660 SCV000260456 uncertain significance Fanconi anemia, complementation group O 2015-09-04 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 320 of the RAD51C protein (p.Lys320Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases and has not been reported in the literature. The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. In addition, 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. In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance.

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