Simple SummaryThe availability of multiple gene panel testing allows us to identify germline pathogenic variants of validated cancer genes. We evaluated the prevalence and clinical/prognostic impact of deleterious germline mutations in OC patients. Germline panel testing should be performed for all patients with ovarian cancer. Better prognosis was found for germline mutated ovarian cancer patients. Endometrioid and clear cell histology subtypes show more deleterious mutations in other genes.AbstractData on deleterious variants in genes other thanBRCA1/2remain limited. A retrospective cohort study was performed, including primary OC cases with TruRisk®germline gene panel testing between 2011 and 2020. Patients with testing after relapse were excluded. The cohort was divided into three groups: (A) no mutations, (B) deleteriousBRCA1/2mutations, and (C) deleterious mutations in other genes. A total of 702 patients met the inclusion criteria. Of these 17.4% (n = 122) showedBRCA1/2mutations and a further 6.0% (n = 42) in other genes. Three-year overall survival (OS) of the entire cohort was significantly longer in patients with germline mutations (85%/82.8% for cohort B/C vs. 70.2% for cohort A,p< 0.001) and 3-year progression-free survival (PFS) only for cohort B (58.1% vs. 36.9%/41.6% in cohort A/C,p= 0.002). In multivariate analysis for the subgroup of advanced-stages of high-grade serous OC, both cohorts B/C were found to be independent factors for significantly better outcome, cohort C for OS (HR 0.46; 95% CI 0.25–0.84), and cohort B for both OS and PFS (HR 0.40; 95% CI 0.27–0.61 and HR 0.49; 95% CI 0.37–0.66, respectively). Germline mutations were detected in a quarter of OC patients, and a quarter of those in genes other thanBRCA1/2. Germline mutations demonstrate in our cohort a prognostic factor and predict better prognosis for OC patients.