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Gene RAD51C
Variant R258H
Impact List missense
Protein Effect loss of function
Gene Variant Descriptions RAD51C R258H does not lie within any known functional domains of the Rad51c protein (UniProt.org). R258H rescues survival in Rad51c-null cells in culture (PMID: 36099300), however, results in variable interaction with Rad51b, Rad51d, and Xrcc3 in a yeast assay (PMID: 36099300), defects in cell cycle progression at the G2/M transition (PMID: 22167183, PMID: 20400963), decreased sensitivity to mitomycin in cell culture, and reduced homologous recombination activity in a reporter assay (PMID: 22167183) and in cell culture (PMID: 36099300).
Associated Drug Resistance
Category Variants Paths

RAD51C mutant RAD51C inact mut RAD51C R258H

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Transcript NM_058216.3
gDNA chr17:g.58709926G>A
cDNA c.773G>A
Protein p.R258H
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_006722001.4 chr17:g.58709926G>A c.773G>A p.R258H RefSeq GRCh38/hg38
XM_006722002.5 chr17:g.58709926G>A c.773G>A p.R258H RefSeq GRCh38/hg38
XM_006722001.5 chr17:g.58709926G>A c.773G>A p.R258H RefSeq GRCh38/hg38
NM_058216.2 chr17:g.58709926G>A c.773G>A p.R258H RefSeq GRCh38/hg38
XM_006722002.4 chr17:g.58709926G>A c.773G>A p.R258H RefSeq GRCh38/hg38
NM_058216.3 chr17:g.58709926G>A c.773G>A p.R258H RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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 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 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 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 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 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
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 breast cancer not applicable N/A Guideline Risk Factor Germline RAD51C mutations are associated with increased risk of developing breast cancer (NCCN.org). detail...