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Extension#

Extension: a sequence change extending the reference amino acid sequence at the N- or C-terminal end with one or more amino acids.

Syntax#

N-terminus extension
Syntax sequence_identifier ":p.Met1ext" new_initiation_site
Examples
  • NP_003997.2:p.Met1ext-5
C-terminus extension
Syntax sequence_identifier ":p.Ter" aa_position aa "extTer" extension_length
Examples
  • NP_003997.2:p.Ter110GlnextTer17
Explanation of Symbols
  • aa: A single amino acid
  • aa_position: A position in a protein sequence. Unlike nucleic acid sequences, protein coordinates are always prefixed with the reference amino acid at that position. (e.g., Lys23)
  • extension_length: The number of amino acids added beyond the original Ter
  • new_initiation_site: The position of the new initiation site; it is always a negative value
  • sequence_identifier: an identifier for a sequence from a recognized database
See also explanation of grammar used in HGVS Nomenclature.

Notes#

  • all variants should be described on the DNA level; descriptions on the RNA and/or protein level may be given in addition.
  • 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) frameshift or deletion-insertion.

Examples#

  • 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), inserting amino acids ArgSerThrVal between Met1 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 of the added sequence.

  • p.Ter327ArgextTer? (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 Ter?) since the shifted frame does not contain a new stop codon.

Discussion#

How are variants on 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 on 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.

How do I describe an extension when no new stop codon is reached?

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?

The description on the DNA-level is, e.g., c.-23A>T (changing CAGGGT to CATGGT, creating a new ATG-triplet). The description on the RNA-level is r.-23a>u, and on 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 frameshift or as an extension?

The variant extends the amino acid sequence at the C-terminal end and is therefore by definition an extension.