Protein Recommendations

Deletion-insertion Variant


Definitions

Deletion-insertion (delins)
a sequence change 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 or conversion.

Description

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

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


Note

  • 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.
  • for all descriptions the most C-terminal position possible of the reference sequence is arbitrarily assigned to have been changed (3’rule)
  • two variants separated by one or more amino acids should preferably be described individually and not as a “delins”
    NOTE : when either of two directly flanking variants is known as a regularly occurring variant, the variants are described individually and not as a “delins”.
  • 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)).
  • when describing the deletion of the “delins”, the description should not extend beyond the sequence affected at the DNA level.
  • in-frame deletion-insertion variants containing a translation termination (stop) codon should be described as a deletion-insertion replacing the affected with the new amino acid sequence (not as a deletion-insertion replacing the entire C-terminus of the protein from the variant site with a new amino acid sequence)
  • frame shifting deletion-insertion variants are a special type of protein variants described as a frame shift (see Frame shift)
    NOTE : deletions at DNA/RNA level that go beyond the translation termination (stop) codon are described as Deletion-insertion, not as frame shift NOTE : insertions from intron sequences which maintain the normal open reading are described as deletion-insertion or Insertion, intronic insertions which give premature translation termination are described as frame shifts
  • deletion/insertion variants in the translation termination (stop) codon, extending the reading frame, are described as Extension. Deletion/insertion variants starting 5’ of and including the translation termination (stop) codon are described as Frame shift.

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
  • p.(Pro578_Lys579delinsLeuTer)
    the predicted change at the protein level resulting from DNA variant c.1733_1735delinsTTT is a deletion of amino acids Pro578 and Lys579 replaced with LeuTer
    NOTE: the predicted consequence of variant c.1732_1794del is p.(Pro578_Gln598del). Although the proteins resulting from the changes c.1733_1735delinsTTT and c.1732_1794del are identical, their HGVS description is different. Example derives from the SLC34A3 gene, coding DNA reference sequence NM_080877.2)
  • 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 (inversion descriptions 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).