Table 1.

Classes of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene according to the traditional classification system.

Class of Mutation	CFTR Molecular Defect	Functional Abnormal Consequence	Mutation Examples	Type of Mutations	Clinical Phenotype	Therapeutic Strategy
I	No mRNA and protein synthesis	Absent protein	G542X, R553X, W1282X	Nonsense, frameshift, canonical splicing	Severe	Read-through agents
II	Reduced protein processing and traffic	Misfolded protein	F508del, N1303K, I507del	Missense, aminoacid deletion,	Severe	Correctors
III	Impaired channel gating	Reduced or absent channel opening	S549N, G551D	Missense, aminoacid change	Severe	Potentiators
IV	Decreased channel conductance	Defect in ion transport	R347P, R117H, D1152H	Missense, amino acid change	Mild	Potentiators
V	Reduced protein synthesis	Decreased protein	3849 + 10 kb C>T, A455E	Splicing defect, missense	Mild	Potentiators, correctors, ASOs
VI	Less protein stability and protein turnover at cell surface	Decreased half-life of the protein	120del23, G1412X	Missense, aminoacid change	Mild	Stabilisers

ASOs, antisense oligonucleotides; CFTR, cystic fibrosis transmembrane conductance regulator.