A new UK NHS bioinformatics framework provides updated best-practice recommendations for high-throughput sequencing in rare disease and cancer diagnosis. Addressing the full diagnostic pipeline, from data quality to interpretation and knowledge sharing, it provides a practical foundation for more consistent and equitable clinical genomics. It aligns bioinformatics practice with the growing scale and complexity of genomic medicine. (https://jmg.bmj.com/content/early/2026/04/29/jmg-2025-111289)