Although, by definition, individually rare, the cumulative burden of ‘rare disease’ is significant, with as many as 3m affected individuals in the UK. The University of Manchester (UoM) has an exceptional record in rare disease gene identification, with 29 such genes defined since 1993. This research paved the way for clinical diagnostic testing for patients and their families, demonstrating the immediate translational impact of gene discovery. The research has resulted in a reduced diagnostic burden for patients and health services and has enabled the provision of more effective counselling. Testing for genes identified at UoM is now offered in more than 140 laboratories in more than 30 countries worldwide. More than 1,100 patients have been tested for mutations in TCOF1, BEST1, IRF6, SAMHD1 and C9ORF72 in UK NHS laboratories alone.