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Gene | RAD51C |
Variant | S105* |
Impact List | nonsense |
Protein Effect | loss of function - predicted |
Gene Variant Descriptions | RAD51C S105* results in a premature truncation of the Rad51c protein at amino acid 105 of 376 (UniProt.org). S105* has not been characterized however, due to the effects of other truncation mutations downstream of S105 (PMID: 28588062), is predicted to lead to a loss of Rad51c protein function. |
Associated Drug Resistance | |
Category Variants Paths |
RAD51C mutant RAD51C inact mut RAD51C S105* |
Transcript | NM_058216.3 |
gDNA | chr17:g.58695099C>A |
cDNA | c.314C>A |
Protein | p.S105* |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_058216 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
XM_047436505.1 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
XM_006722001.5 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
XM_006722001 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
XM_006722002.5 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
NM_058216.3 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
XM_006722001.4 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
XM_006722002.4 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
NM_002876.4 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
NM_002876 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
NM_002876.3 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
XM_006722002 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
NM_058216.2 | chr17:g.58695099C>A | c.314C>A | p.S105* | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
RAD51C inact mut | Advanced Solid Tumor | sensitive | E7449 | Preclinical | Actionable | In a preclinical study, E7449 inhibited proliferation of a RAD51C-deficient cell line in culture, which demonstrated increased sensitivity compared to cells without DNA repair pathway mutations (PMID: 26513298). | 26513298 |
RAD51C inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | Guideline | Actionable | Talzenna (talazoparib) plus Xtandi (enzalutamide) is included in guidelines as systemic therapy for patients with metastatic castration-resistant prostate cancer harboring a pathogenic germline or somatic RAD51C mutation who have not been treated in the setting of castration-resistant prostate cancer (NCCN.org). | detail... |
RAD51C inact mut | prostate cancer | sensitive | Enzalutamide + Talazoparib | FDA approved | Actionable | In a Phase III trial (TALAPRO-2) that supported FDA approval, Talzenna (talazoparib) plus Xtandi (enzalutamide) improved median radiographic progression-free survival compared to enzalutamide plus placebo (27.9 vs 16.4 mo, HR 0.46, p=0.0003) in patients with metastatic castration-resistant prostate cancer harboring deficient homologous recombination repair genes including RAD51C, HR was 0.66 (p=0.12) in patients with non-BRCA mutations treated with Talzenna (talazoparib) (PMID: 37285865; NCT03395197). | 37285865 detail... |
RAD51C inact mut | ovarian cancer | predicted - sensitive | RP-3500 | Case Reports/Case Series | Actionable | In a Phase I/II trial (TRESR), RP-3500 treatment resulted in a partial response with complete resolution of the target lesion at 19 weeks in a patient with ovarian cancer harboring a RAD51C inactivating mutation (PMID: 37277454; NCT04497116). | 37277454 |
RAD51C inact mut | prostate cancer | sensitive | Olaparib | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (PROfound) that supported FDA approval, Lynparza (olaparib) treatment significantly improved median imaging-based progression-free survival (5.8 vs 3.5 mo, HR 0.49, p<0.001) compared to control in patients with metastatic castration-resistant prostate cancer who progressed on hormone therapy and harbored deleterious or suspected deleterious mutations in homologous recombination repair genes, including RAD51C (PMID: 32343890; NCT02987543). | detail... detail... 32343890 |
RAD51C inact mut | prostate cancer | sensitive | Olaparib | Guideline | Actionable | Lynparza (olaparib) is included in guidelines as second-line therapy post androgen receptor-directed therapy for patients with metastatic castration-resistant prostate cancer harboring pathogenic mutations in RAD51C (NCCN.org). | detail... |
RAD51C mutant | breast cancer | not applicable | N/A | Guideline | Risk Factor | Germline RAD51C mutations are associated with increased risk of developing breast cancer (NCCN.org). | detail... |
RAD51C mutant | ovarian cancer | not applicable | N/A | Guideline | Risk Factor | Germline RAD51C mutations are associated with increased risk of developing ovarian cancer (NCCN.org). | detail... |
RAD51C mutant | ovarian serous carcinoma | predicted - sensitive | Olaparib | Case Reports/Case Series | Actionable | In a clinical case study, Lynparza (olaparib) treatment resulted in a complete response with treatment ongoing at 14 months in a patient with relapsed, metastatic high grade serous ovarian carcinoma harboring RAD51C mutations (PMID: 36176748). | 36176748 |