The removal or addition of one or more nucleotides which severely disrupts the production of the protein, e.g. some Duchenne muscular dystrophy mutations. The result of this is that the protein produced is completely non-functional or not produced at all. Also known as 'frame-shift mutation'. See also In-frame mutation. For a more in-depth explanation please see our FAQ 'What is exon skipping and how does it work?'.