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 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.
  • two variants separated by one or more amino acids should preferably be described individually and not as a “delins”
  • frame shifting deletion/insertion variants are a special type of protein variants described as a frame shift (see Frame shift)
  • for all descriptions the most C-terminal position possible of the reference sequence is arbitrarily assigned to have been changed (3’rule)

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 "delins"?

An "delins", insertion/deletion in HGVS nomenclature, is a variant which is a combination of a deletion and an insertion. Based on existing nomeclature, the variant can be described as a deletion and insertion occuring at the same position, using the format p.Asn112_Thr117delinsSerAsp.

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).