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English: Exon Skipping caused by an acceptor mutation in the gene MLH1 leading to colorectal cancer. The generation of a mRNA from a split gene involves the transcription of the gene into a primary RNA transcript, and the precise removal of the introns and the joining of the exons from the primary RNA transcripts. A deleterious mutation within the splicing signals (donor or acceptor splice sites) can affect the recognition of the correct splice junction and lead to an aberration in the joining of the authentic exons. Depending on if the mutation occurs within the donor or the acceptor site, and the particular base that is mutated within the site, the aberration could lead to the skipping of a complete or partial exon, or the inclusion of a partial intron or a cryptic exon in the mRNA produced by the splicing process. Either of these situations will usually lead to a premature stop codon in the mRNA and result in a completely defective protein. The S&S algorithm aids in the determination of which splice site and exon is mutated, and the S&S score of the mutated splice site aids in the determination of the type of splicing aberration and the mRNA structure and sequence. The example of the gene MLH1 affected in colorectal cancer is shown in the figure. It was found using the S&S algorithm that a mutation in the donor splice site in exon 8 led to the skipping of the exon 8. The mRNA thus lacks the sequence corresponding to exon 8 (sequence positions are shown in the figure). This causes a frame shift leading to the premature protein truncation at amino acid position 204. This mutated protein is completely defective, which has led to colorectal cancer in the patient. This mutated protein is completely defective, which has led to colorectal cancer in the patient.