Protein Recommendations

Deletion-insertion Variant


Definitions

Deletion-insertion (delins)
a sequence change between the translation initiation (start) and termination (stop) codon where, compared to a reference sequence, one or more amino acids are replaced with one or more other amino acids and which is not a substitution, frame shift or conversion.

Description

Format: “prefix”“amino_acid(s)+position(s)_deleted”“delins”“inserted_sequence”, e.g. p.(Arg123_Lys127delinsSerAsp)

“prefix” = reference sequence used = p.
“amino_acid(s)+position(s)_deleted” = position amino acid or range of amino acids deleted = Arg123_Lys127
“delins” = type of change is a deletion-insertion = delins
“inserted_sequence” = description inserted sequence = SerAsp


Note

  • 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).
  • by definition, when one amino acid is replaced with one other amino acid, the change is a substitution, not a deletion-insertion.
  • for all descriptions the most C-terminal position possible of the reference sequence is arbitrarily assigned to have been changed (3’rule)
  • predicted consequences, i.e. without experimental evidence (no RNA or protein sequence analysed), should be given in parentheses, e.g. p.(Arg123_Lys127delinsSerAsp).
  • when the inserted protein sequence is large and it is possible to derive the inserted amino acid sequence from the description given at DNA or RNA level, the insertion may be described by its length only (e.g. p.Arg456_Leu488delins(54)).
  • two variants separated by one or more amino acids should preferably be described individually and not as a “delins”
  • changes involving two or more consecutive amino acids are described as a deletion/insertion variant (delins)
    • NOTE: this does not mean that at the DNA level the variant is described as a “delins” variant as well; on DNA level other rules may apply
  • variants should be described on the protein level and not incorporate knowledge regarding the change at the DNA level.
    • deletion-insertion variants containing a translation stop codon in the inserted sequence are described as deletion-insertion of this sequence, not as a deletion-insertion removing the entire C-terminal amino acid sequence
    • deletion-insertion variants encoding an open reading frame which after the inserted sequence shift to another reading frame are described as a frame shift
    • deletion-insertion variants starting N-terminal (5’) of and including the translation termination (stop) codon are described as frame shift. * deletion/insertion variants extending the full-length amino acid sequence at the C-terminal end with one or more amino acids are described as Extension.

Examples

  • p.Cys28delinsTrpVal
    a deletion of amino acid Cys28, replaced with TrpVal
  • p.Cys28_Lys29delinsTrp
    a deletion of amino acids Cys28 and Ly29, replaced with Trp
  • NP_004371.2:p.(Asn47delinsSerSerTer)
    the predicted change at the protein level resulting from DNA variant NM_004380.2:c.139delinsTCATCATGAGCTG is a deletion of amino acid Asn47 replaced with SerSerTer (alternatively SerSer*).
    NOTE: the deletion-insertion is not described as “delinsSerSerTerAlaAsp”, amino acids after the translation termination codon are not listed.
  • p.(Pro578_Lys579delinsLeuTer)
    the predicted change at the protein level resulting from DNA variant NM_080877.2c.1733_1735delinsTTT is a deletion of amino acids Pro578 and Lys579 replaced with LeuTer (alternatively Leu*)
    NOTE: the predicted consequence of variant NM_080877.2:c.1732_1794del is p.(Pro578_Gln598del). Although the proteins resulting from the changes NM_080877.2:c.1733_1735delinsTTT and c.1732_1794del are identical, their HGVS description is different. NOTE: example derives from the SLC34A3 gene.
  • NP_000213.1:p.(Val559_Glu561del)
    the predicted change at the protein level resulting from DNA variant NM_000222.3:c.1676_1684del. The variant is not described as p.(Val559_Glu562delinsGlu), where Glu562 would be replaced by a Glu which effectively is no change. Example derives from the KIT gene.
  • NP_003070.3:p.(Glu125_Ala132delinsGlyLeuHisArgPheIleValLeu)
    the predicted change at the protein level resulting from DNA variant NM_003079.4:c.374_395inv is a deletion of amino acids Glu125 to Ala132 replaced with GlyLeuHisArgPheIleValLeu.
    NOTE: the predicticted consequence from the inversion on DNA level is described as a deletion-insertion (inversions are not used at protein level)
  • p.[Ser44Arg;Trp46Arg]
    the change of two variants affecting amino acids separated by another amino acid.
    NOTE: the variant is not described as p.Ser44_Trp46delinsArgLeuArg

Q&A

What is an "indel"?

The term "indel" is not used in HGVS nomenclature (see Glossary). The term is confusing, having different meanings in different disciplines.

Can I describe a TrpSer to CysArg variant as a amino acid substitution (p.TrpSer23CysArg)?

No, this is not allowed. By definition a substitution changes one amino acid into one other amino acid. The change TrpSer to CysArg should be described as p.Trp23_Ser24delinsCysArg, i.e. a deletion/insertion (indel) (see Deletion-Insertion).