Radboud University Medical Center began running long‑read whole‑genome sequencing (WGS) as a frontline diagnostic for genetic eye disease and severe intellectual disability, replacing multiple traditional assays such as karyotyping, microarrays and targeted panels. The center will analyze up to 5,000 genomes in the next year using Pacific Biosciences’ long‑read platform, a major clinical endorsement for the technology. The implementation follows a prospective 1,000‑sample comparison showing long reads can consolidate disparate testing modalities into a single assay with improved structural‑variant detection. Radboud scientists aim to scale to 25,000 genomes per year across regional centers as part of a national effort to offer genome‑first diagnostics for rare disease patients. Clinical labs and sequencing vendors should view the rollout as a pivotal commercial inflection: payers, diagnostic labs and referral centers will monitor diagnostic yield, turnaround time, and cost per diagnosis as long‑read WGS seeks broader clinical adoption.