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. 2022 Jul 8;3(9):1640–1651. doi: 10.34067/KID.0007552021

Table 1.

Types of variants resulting from single or small oligonucleotide variants

Variant Type Definition Nucleotide Change Coding DNA Nomenclature “c. prefix” Protein Nomenclature “p. prefix” Comments Implication
Substitution (synonymous) Single nucleotide substitution resulting in unchanged AA c.6A>G p.Arg2=
or p.Arg2Arg

  • • 6th nucleotide adenine changed to guanine

  • • Variant occurs at 2nd codon; both AGA and AGG encode arginine to the protein sequence is not affected

 No change in AA; likely benign unless near splice junction
Substitution (missense) Single nucleotide substitution changing AA c.5G>T p.Arg2Ile

  • • 5th nucleotide guanine changed to thymine

  • • 2nd codon encoded arginine, but variant encodes isoleucine (Ile)

 AA changed; potentially pathogenic if significant change in important AA
Substitution (nonsense) Single nucleotide substitution creating a stop codon c.4A>T p.Arg2Ter
or p.Arg2X

  • • 4th nucleotide adenine changed to thymine

  • • 2nd codon encoded arginine, but variant encodes a premature stop codon

 Truncated protein; pathogenic in majority of disease mechanisms
Insertion/deletion (frame shift) Insertion or deletion of # nucleotides (# ≠ multiple of 3) c.4delA p.Arg2fs

  • • 4th nucleotide adenine is deleted

  • • A resultant shift in the reading frame no longer encodes the intended protein and by chance will reach a stop codon

 Truncated/altered protein; all AAs distal to frame shift are changed; pathogenic in majority of disease mechanisms
Insertion/deletion (nonframeshift) Insertion or deletion of # nucleotides (# = multiple of 3) c.4_6delAGA p.Arg2del

  • • 4th through 6th nucleotides are deleted, causing loss of the Arg but no frameshift

 AA deleted; potentially pathogenic if critical AA
Substitution (splice variant) Single nucleotide substitution c.21 + 1G>T

  • • 1st intronic nucleotide (guanine) is changed to a thymine; no protein consequence is defined given intronic variant

 Truncated protein expected; splice site abolished if first or second intronic base is modified; pathogenic in majority of disease mechanisms

AA, amino acid.