When the CFTR gene and the major disease-causing mutation c.1521-1523delCTT (F508del; ~70% of CF alleles and found in ~85% of PwCF) were first described in 1989 [39,40,41], it was proposed that multiple mutations would make up the remaining 30% of CF alleles. The gene discussed is CFTR; the disease is cystic fibrosis.