• Severity of damage: silent << missense < nonsense < frameshift.
• For point (silent, missense, and nonsense) mutations:
  • Transition—purine to purine (eg, A to G) or pyrimidine to pyrimidine (eg, C to T).
  • Transversion—purine to pyrimidine (eg, A to T) or pyrimidine to purine (eg, C to G).
• Silent
  • Nucleotide substitution but codes for same (synonymous) amino acid; often base change in 3rd position of codon (tRNA wobble).
• Missense
  • Nucleotide substitution resulting in changed amino acid (called conservative if new amino acid is similar in chemical structure).
  • Sickle cell disease (substitution of glutamic acid with valine).
• Nonsense
  • Nucleotide substitution resulting in early stop codon (UAG, UAA, UGA). Usually results in nonfunctional protein.
  • Stop the nonsense!
• Nonstop
  • Base substitution within stop code results in continued translation.
• Frameshift
  • Deletion or insertion of a number of nucleotides not divisible by 3, resulting in misreading of all nucleotides downstream. Protein may be shorter or longer, and its function may be disrupted or altered.
  • Duchenne muscular dystrophy, Tay-Sachs disease.
• Splice site
  • Mutation at a splice site → retained intron in the mRNA → protein with impaired or altered function.
  • Rare cause of cancers, dementia, epilepsy, some types of β-thalassemia.
• Conservative
  • Base substitution codes for different amino acid with similar chemical structure