Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000533764 | SCV000650030 | uncertain significance | Fanconi anemia complementation group O | 2022-07-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 322 of the RAD51C protein (p.Arg322Thr). This variant also falls at the last nucleotide of exon 7, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 471453). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Ambry Genetics | RCV001019608 | SCV001180989 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-23 | criteria provided, single submitter | clinical testing | The c.965G>C variant (also known as p.R322T), located in coding exon 7 of the RAD51C gene, results from a G to C substitution at nucleotide position 965. The amino acid change results in arginine to threonine at codon 322, an amino acid with similar properties. However, this change occurs in the last base pair of coding exon 7, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species, and this amino acid position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003459249 | SCV004207974 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-08-01 | criteria provided, single submitter | clinical testing |