Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000130508 | SCV000185377 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-26 | criteria provided, single submitter | clinical testing | The p.L323W variant (also known as c.968T>G), located in coding exon 8 of the RAD51C gene, results from a T to G substitution at nucleotide position 968. The leucine at codon 323 is replaced by tryptophan, an amino acid with similar properties. This alteration has been previously detected in a cohort of 381 unselected endometrial cancer patients who underwent multi-gene panel testing (Ring KL et al. Mod. Pathol., 2016 11;29:1381-1389). This amino acid position is well 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. |
| Invitae | RCV000475164 | SCV000550197 | uncertain significance | Fanconi anemia complementation group O | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 323 of the RAD51C protein (p.Leu323Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with endometrial cancer (PMID: 27443514). ClinVar contains an entry for this variant (Variation ID: 141835). 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 tolerated. 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. |
| Gene |
RCV000484566 | SCV000568042 | uncertain significance | not provided | 2023-08-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in an individual with endometrial cancer in published literature (Ring et al., 2016); This variant is associated with the following publications: (PMID: 14704354, 27443514) |
| Color Diagnostics, |
RCV000130508 | SCV000686411 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-16 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with tryptophan at codon 323 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 been reported in an individual affected with endometrial cancer (PMID: 27443514). This variant has been identified in 1/251368 chromosomes 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000484566 | SCV001134796 | uncertain significance | not provided | 2018-10-08 | criteria provided, single submitter | clinical testing |