Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220031 | SCV000275300 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-04-23 | criteria provided, single submitter | clinical testing | The p.C335* variant (also known as c.1005C>A), located in coding exon 8 of the RAD51C gene, results from a C to A substitution at nucleotide position 1005. This changes the amino acid from a cysteine to a stop codon within coding exon 8. This alteration occurs at the 3' terminus of RAD51C gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 11% of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV000232127 | SCV000291208 | likely pathogenic | Fanconi anemia complementation group O | 2024-03-07 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys335*) in the RAD51C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the RAD51C protein. This variant is present in population databases (rs759292615, gnomAD 0.006%). 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: 231450). This variant disrupts the nuclear localization signal (NLS) of the RAD51C protein, which is important for proper localization and function of the RAD51C protein (PMID:12966089). While functional studies have not been performed to directly test the effect of this variant on RAD51C protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Gene |
RCV000657741 | SCV000779492 | likely pathogenic | not provided | 2020-01-02 | criteria provided, single submitter | clinical testing | Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 42 amino acids are lost including the nuclear localization signal (French 2003); Not observed at a significant frequency in large population cohorts (Lek 2016); Has not been previously published as pathogenic or benign to our knowledge |