Figure 1

Diagnostic trajectory and resulting diagnostic yield and costs per patient for standard care and for integrating singleton whole-exome sequencing (WES) using three models. In model 1, standard investigations are exhausted first, including all planned tests, resulting in an additional six diagnoses (a total of 13), and WES is performed as a last resort for patients who remain undiagnosed. In model 2, WES replaces some investigations, particularly gene sequencing tests, complex biochemical tests, and invasive tests. In model 3, WES replaces most investigations. Dx, diagnosis.