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deletion-insertion

Definition

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

Notes

  • 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).
  • 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 with 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) (see Substitution.
    • NOTE: this does not mean that at 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 od the variant at 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 Extension.
  • deletion-insertion variants at the DNA or RNA level.
    • which introduce an immediate translation termination (stop) codon at the protein level are described as a nonsense variant, e.g. p.Tyr4Ter (or p.Tyr4*) not p.Cys5_Ser6delinsTerGluAsp.
    • encoding 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.
    • encoding an open reading frame which after the inserted sequence shift to another reading frame are described as a frame shift.
    • starting N-terminal (5') of and including the translation termination (stop) codon are described as frame shift.
  • fusion proteins represent a special case of deletion-insertion variant. The fusion break point is described using "::": NOTE: to avoid confusion, HGVS recommends to follow the HGNC guidelines to describe products of gene translocations or fusions (format GENESYMBOL1::GENESYMBOL2) and readthrough transcripts (format GENESYMBOL1-GENESYMBOL2)

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

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 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).