ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.164C>T (p.Ala55Val) (rs730881928)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214683 SCV000278015 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000214683 SCV000909438 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-24 criteria provided, single submitter clinical testing
GeneDx RCV000759333 SCV000211623 uncertain significance not provided 2016-07-22 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.164C>T at the cDNA level, p.Ala55Val (A55V) at the protein level, and results in the change of an Alanine to a Valine (GCA>GTA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Ala55Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Alanine and Valine share similar properties, this is considered a conservative amino acid substitution. RAD51C Ala55Val occurs at a position that is not conserved and is located within the region required for Holliday junction resolution activity (UniProt). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether RAD51C Ala55Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000648250 SCV000770064 uncertain significance Fanconi anemia, complementation group O 2018-12-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 55 of the RAD51C protein (p.Ala55Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 182831). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759333 SCV000888593 uncertain significance not provided 2018-03-13 criteria provided, single submitter clinical testing

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