Extension: a sequence change extending the reference amino acid sequence at the N- or C-terminal end with one or more amino acids.
Format (N-terminal): "prefix""Met1""ext""position_new_initiation_site", e.g. p.Met1ext-5
"prefix" = reference sequence used = p. "Met1" = normal translation initiation site = Met1 "ext" = type of change is an extension = ext "position_new_initiation_site" = position new upstream translation initiation site = -5
Format (C-terminal): "prefix""Ter_position""new_amino_acid""ext""Ter""position_new_termination_site", e.g. p.Ter110GlnextTer17
"prefix" = reference sequence used = p. "Ter_position" = normal translation termination site = Ter110 "new_amino_acid" = amino acid encoded by variant termination codon = Gln "ext" = type of change is an extension = ext "Ter" = termination codon = Ter / * "position_new_termination_site" = position new downstream translation termination site = 17
- all variants should be described at the DNA level, descriptions at the RNA and/or protein level may be given in addition
- prefix reference sequence accepted is "p." (protein).
- extension variants have been accepted on 2012-08-31.
- predicted consequences, i.e. without experimental evidence (no RNA or protein sequence analysed), should be given in parentheses, e.g. p.(Ter110GlnextTer17) or p.(*110Glnext*17).
- variants affecting the translation initiation site (Met1) activating an upstream (N-terminal) translation initiation site are described as deletion-insertion, those activating a downstream (C-terminal) initiation site as a deletion.
- prioritisation: (1) extension, (2) frame shift or deletion-insertion.
- p.Met1ext-5: a variant in the 5' UTR activates a new upstream translation initiation site starting with amino acid Met-5: NOTE: modified from p.Met1extMet-5
- p.Met1_Leu2insArgSerThrVal: amino acid Met1 is changed to Val activating an upstream translation initiation site at position -4 (Met-4), insertion amino acids ArgSerThrVal between Mat1 and Leu2.: NOTE: this variant is not described as an extension (p.Met1Valext-4) since Met1, part of the normal amino acid sequence, is changed
- p.Ter110GlnextTer17 (alternatively p.*110Glnext*17): a variant in the stop codon (Ter/*) at position 110, changing it to a Gln-codon (a no-stop variant) and adding a tail of new amino acids to the protein's C-terminus, ending at a new stop codon (Ter/*) at position 17
- p.Ter327Argext*? (alternatively p.*327Argext*?): a variant in the stop codon (Ter/*) at position 327, changing it to an Arg-codon and adding a tail of new amino acids of unknown length (position *?) since the shifted frame does not contain a new stop codon.
How are variants at the protein level called that directly affect the translation initiation (start) codon?
The variant is called start-lost variant, one of two types of a protein extension, an N-terminal extension. Note the difference with a start-gained variant where the start codon itself is not directly affected, another type of N-terminal extension.
How are variants at the protein level called that directly affect the translation termination (stop) codon?
The variant is called a no-stop or stop-lost variant, one of two types of a protein extension, a C-terminal extension.
Such variants are described using the format p.Ter789ArgextTer?, i.e. "extTer?" to indicate that no new termination codon is encountered.
How should a variant in the 5'UTR be described that gives rise to a new translation initiation site?
Description at the DNA-level is like c.-23A>T (changing c.-25 caGggt c.-19 to caTggt, creating a new ATG-triplet). Description at the RNA-level is r.-23a>u and at the protein level p.(Met1ext-8), indicating the predicted protein sequence is an N-terminal extension with 8 amino acids.
Should I describe a duplication in the translation termination codon (TGA to TGGA) as a frame shift or as an extension?
The variant extends the amino acid sequence at the C-terminal end and is therefore by definition an extension.