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Deletion-Insertion#

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 by one or more other amino acids and which is not a substitution or frameshift.

Syntax#

single position
Syntax sequence_identifier ":p." aa_position "delins" sequence
Examples
  • NP_004371.2:p.Asn47delinsSerSerTer
  • NP_004371.2:p.(Asn47delinsSerSerTer)
position range
Syntax sequence_identifier ":p." aa_position "_" aa_position "delins" sequence
Examples
  • NP_003070.3:p.Glu125_Ala132delinsGlyLeuHisArgPheIleValLeu
Explanation of Symbols
  • 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)
  • sequence: DNA, RNA, or AA sequence
  • 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.(Arg123_Lys127delinsSerAsp).
  • by definition, when one amino acid is replaced by one other amino acid, the change is a substitution, not a deletion-insertion.
  • changes involving two or more consecutive amino acids are described as a deletion/insertion variant (delins).
    • NOTE: this does not mean that on the DNA or RNA level the variant is described as a "delins" variant as well; on DNA level, other rules may apply.
    • the description p.Arg76_Cys77delinsSerTrp is correct, the description p.[Arg76Ser;Cys77Trp] is not correct.
    • two variants separated by one or more amino acids should be described individually and not as a "delins".
  • for all descriptions, the most C-terminal position possible of the reference sequence is arbitrarily assigned to have been changed (3'rule).
  • when the inserted amino acid sequence is large, the insertion may be described by its length, e.g., p.Lys2_Leu3insX[34] (open reading frame insertion) or p.Lys2_Leu3insTer12 (translation stop in inserted sequence).
    NOTE: the inserted amino acid sequence can be derived from the description of the variant on the DNA or RNA level.
  • deletion/insertion variants extending the full-length amino acid sequence at the C-terminal end with one or more amino acids are described as an Extension.
  • deletion-insertion variants on the DNA or RNA level that
    • introduce an immediate translation termination (stop) codon on the protein level, are described as a nonsense variant, e.g., p.Tyr4Ter (or p.Tyr4*), not p.Cys5_Ser6delinsTerGluAsp.
    • encode 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.
    • encode an open reading frame which after the inserted sequence shifts to another reading frame, are described as a frameshift.
    • start N-terminal (5') of and including the translation termination (stop) codon, are described as frameshift.
  • chimeric proteins represent a special case of deletion-insertion variant. The protein sequence junction is described using ::.
    NOTE: to avoid confusion, HGVS recommends to follow the HGNC guidelines, VICC Gene Fusion Specification, and adjoined transcripts to describe the products of gene fusions.

Examples#

  • p.Cys28delinsTrpVal
    a deletion of amino acid Cys28, replaced by TrpVal.

  • p.Cys28_Lys29delinsTrp
    a deletion of amino acids Cys28 and Lys29, replaced by Trp.

  • NP_004371.2:p.(Asn47delinsSerSerTer)
    the predicted change on the protein level resulting from DNA variant NM_004380.2:c.139delinsTCATCATGAGCTG is a deletion of amino acid Asn47 replaced by 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 on the protein level resulting from DNA variant NM_080877.2c.1733_1735delinsTTT is a deletion of amino acids Pro578 and Lys579 replaced by 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. Example derived from the SLC34A3 gene.

  • NP_000213.1:p.(Val559_Glu561del)
    the predicted change on 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 derived from the KIT gene.

  • NP_003070.3:p.(Glu125_Ala132delinsGlyLeuHisArgPheIleValLeu)
    the predicted change on the protein level resulting from DNA variant NM_003079.4:c.374_395inv is a deletion of amino acids Glu125 to Ala132 replaced by GlyLeuHisArgPheIleValLeu.
    NOTE: the predicted consequence of the inversion on DNA level is described as a deletion-insertion (inversions are not used on 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.

Discussion#

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 TrpVal to CysArg variant as a amino acid substitution (p.TrpVal24CysArg)?

No, this is not allowed. By definition, a substitution changes one amino acid into one other amino acid. The change TrpVal to CysArg should be described as NP_003997.1:p.Trp24_Val25delinsCysArg, i.e. a deletion/insertion (delins).