CFTR and cystic fibrosis: Clinical classification depends on the severity of the most frequently associated phenotype when the patients carry a severe mutation in trans: CF causing mutations are responsible for classical cystic fibrosis mainly with pancreatic in sufficiency, CFTR-RD variants retain residual function and are associated to mono-symptomatic disease or milder phenotype, benign variants have no clinical consequences and variants of uncertain clinical significance (VUS) are not yet classified [2].