Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000549809 | SCV000660411 | uncertain significance | Fanconi anemia complementation group O | 2023-06-09 | criteria provided, single submitter | clinical testing | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 478776). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 368 of the RAD51C protein (p.Arg368Gln). |
| Color Diagnostics, |
RCV000579997 | SCV000686321 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-18 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with glutamine at codon 368 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RAD51C-related hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV000579997 | SCV001178390 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.R368Q variant (also known as c.1103G>A), located in coding exon 9 of the RAD51C gene, results from a G to A substitution at nucleotide position 1103. The arginine at codon 368 is replaced by glutamine, an amino acid with highly similar properties. This alteration was identified 1/302 individuals with pancreatic cancer and a positive family history. (Chaffee KG et al. Genet Med, 2018 01;20:119-127). This amino acid position is highly 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001731788 | SCV001983681 | uncertain significance | not specified | 2021-09-20 | criteria provided, single submitter | clinical testing | Variant summary: RAD51C c.1103G>A (p.Arg368Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249298 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1103G>A has been reported in the literature as a VUS in settings of multigene cancer panel testing in at-least one individual affected with pancreatic cancer (example, Chaffee_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Baylor Genetics | RCV003470802 | SCV004208001 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-05-24 | criteria provided, single submitter | clinical testing |