Genetic testing plays a significant role in rare disease diagnostics. Since the rise of next generation sequencing in the last decade the time to diagnosis has become shorter for many patients, ending the so-called diagnostic odyssey. One of the most widely used tools in this category is whole exome sequencing (WES). Our laboratory performed diagnostic WES on 1660 samples representing 825 index patients between 2014 and 2020. This retrospective study aims to review lessons that can be drawn from this cohort and describes diagnostic yield in general as well as for subgroups defined by age, phenotype and more.825 patients received a full diagnostic WES analysis. Patients’ symptoms were translated to terms in the Human Phenotype Ontology (HPO) system and each symptom assigned to a single top-level HPO term. WES variants were classified according to ACMG-AMP guidelines. Patients were discussed in a multidisciplinary setting to ensure high quality of the reported result.The diagnostic yield in this cohort was 33.7% with 278 patients receiving a genetic diagnosis, which is comparable to similar studies at 25-38%.Patients with complex phenotypes with involvement of several organ systems were more likely to receive a genetic diagnosis. Higher diagnostic yields were seen for phenotypes including growth abnormalities, abnormalities of the ear or of the musculoskeletal system as well.