ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.1005C>A (p.Cys335Ter)

gnomAD frequency: 0.00001  dbSNP: rs759292615
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220031 SCV000275300 likely pathogenic Hereditary cancer-predisposing syndrome 2019-01-29 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 stop codon occurs at the 3' terminus of RAD51C and is not expected to trigger nonsense-mediated mRNA decay, but the truncation disrupts an important functional domain. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV000232127 SCV000291208 likely pathogenic Fanconi anemia complementation group O 2022-12-02 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%). 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. This variant disrupts the p.Cys335 amino acid residue in RAD51C. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12966089). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 231450). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions.
GeneDx 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

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