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 with one or more other amino acids and which is not a substitution, frameshift or conversion.
Syntax#
single position | |
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Syntax | sequence_identifier ":p." aa_position "delins" sequence |
Examples |
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position range | |
Syntax | sequence_identifier ":p." aa_position "_" aa_position "delins" sequence |
Examples |
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Explanation of Symbols | |
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Notes#
- all variants should be described at the DNA level, descriptions at 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 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 descriptionp.[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) orp.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
(orp.Tyr4*
) notp.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 frameshift.
- starting N-terminal (5') of and including the translation termination (stop) codon are described as frameshift.
- which introduce an immediate translation termination (stop) codon at the protein level are described as a nonsense variant, e.g.
- 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 TrpValp.Cys28_Lys29delinsTrp
: a deletion of amino acids Cys28 and Ly29, replaced with TrpNP_004371.2:p.(Asn47delinsSerSerTer)
: the predicted change at the protein level resulting from DNA variantNM_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 variantNM_080877.2c.1733_1735delinsTTT
is a deletion of amino acids Pro578 and Lys579 replaced with LeuTer (alternatively Leu*): NOTE: the predicted consequence of variantNM_080877.2:c.1732_1794del
isp.(Pro578_Gln598del)
. Although the proteins resulting from the changesNM_080877.2:c.1733_1735delinsTTT
andc.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 variantNM_000222.3:c.1676_1684del
. The variant is not described asp.(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 variantNM_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 asp.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).