Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000571191 | SCV000674676 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-09 | criteria provided, single submitter | clinical testing | The p.L226P variant (also known as c.677T>C), located in coding exon 4 of the RAD51C gene, results from a T to C substitution at nucleotide position 677. The leucine at codon 226 is replaced by proline, an amino acid with similar properties. In one study, this variant was reported in 1/3429 patients with epithelial ovarian cancer and 0/2772 controls (Song H et al. J. Clin. Oncol., 2015 Sep;33:2901-7). This variant was also identified in 1/882 Chinese individuals who underwent multi-gene panel testing for HBOC risk assessment (Shao D et al, Cancer Sci., 2020 Feb;111:647-657). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759335 | SCV000888600 | uncertain significance | not provided | 2018-02-22 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001068731 | SCV001233861 | uncertain significance | Fanconi anemia complementation group O | 2022-12-18 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAD51C protein function. ClinVar contains an entry for this variant (Variation ID: 486269). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 26261251, 31742824). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 226 of the RAD51C protein (p.Leu226Pro). |
Gene |
RCV000759335 | SCV001791214 | uncertain significance | not provided | 2020-06-17 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with ovarian cancer (Song 2015); This variant is associated with the following publications: (PMID: 26261251) |
Sema4, |
RCV000571191 | SCV002530003 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | curation |