ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.1102C>T (p.Arg368Trp) (rs587780253)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000116171 SCV000183930 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000116171 SCV000686320 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-05 criteria provided, single submitter clinical testing
Counsyl RCV000662871 SCV000785763 uncertain significance Breast-ovarian cancer, familial 3; Fanconi anemia, complementation group O 2017-11-30 criteria provided, single submitter clinical testing
GeneDx RCV000212951 SCV000150080 uncertain significance not specified 2017-04-07 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.1102C>T at the cDNA level, p.Arg368Trp (R368W) at the protein level, and results in the change of an Arginine to a Tryptophan (CGG>TGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant 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 Arginine and Tryptophan differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51C Arg368Trp occurs at a position that is conserved in mammals and is located in the ATPase domain (Kim 2011). In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether RAD51C Arg368Trp is pathogenic or benign. We consider it to be a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000392360 SCV000404325 uncertain significance Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000302331 SCV000404326 uncertain significance Breast and Ovarian Cancer Susceptibility 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000227763 SCV000291212 uncertain significance Fanconi anemia, complementation group O 2018-08-14 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 368 of the RAD51C protein (p.Arg368Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs587780253, ExAC 0.06%). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 128202). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Mendelics RCV000709519 SCV000839343 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing

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