Some synonymous changes are directly related to the pathogenesis of a disease, e.g., in Treacher-Collins’ syndrome, the synonymous variant c.3612A>C in the TCOF1 gene causes exon 22 skipping and mis-splicing and results in defective mRNA [43], and in cystic fibrosis, a structural instability of mRNA, caused by the synonymous polymorphism p.Ile507Ile in the context of ΔF508 CFTR, could be responsible for the reduced translational rate and lower cellular expression level of CFTR protein [44]. This evidence concerns the gene CFTR and Treacher-Collins syndrome.