1. Classes of mutations affecting CFTR production, structure, and function.

Class	Example mutation	Impact on CFTR structure and function
I	G542X	Synthesis of CFTR is critically impaired, and no functional protein is produced. This is due to the presence of a premature termination codon in the nucleotide sequence. Individuals have no CFTR function.
II	phe508del (ΔF508)	A full length of CFTR is produced, but this is structurally abnormal and destroyed by the cell before it reaches the cell membrane. This is called a defect in the intracellular trafficking pathway. Individuals have no CFTR function under normal conditions.
III	G551D	CFTR is produced and embedded in the cell membrane, but the chloride channel does not respond ('switch on') to normal stimulation from the cell. This means there is no significant ion transport across the protein. Individuals have no CFTR function.
IV	R347P	CFTR is transported to the outer cell membrane, and responds to normal stimulation, but functions at a low level because chloride ions do not cross the channel appropriately. Individuals have some residual CFTR function.
V	A455E	Normal CFTR is produced, but the amount of protein is reduced. Individuals have some residual CFTR function.

CFTR: cystic fibrosis transmembrane conductance regulator