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Deletion#

Deletion: a sequence change between the translation initiation (start) and termination (stop) codon where, compared to a reference sequence, one or more amino acids are not present (deleted).

Syntax#

Single position
Syntax sequence_identifier ":p." aa_position "del"
Examples
  • NP_003997.2:p.Val7del
Position range
Syntax sequence_identifier ":p." aa_position "_" aa_position "del"
Examples
  • NP_003997.2:p.Lys23_Val25del
Alternative view
Syntax sequence_identifier ":p." aa_range "del"
Examples
  • NP_003997.2:p.Lys23_Val25del
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)
  • aa_range: A range of aa_position. (e.g., Lys23_Val25)
  • 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.(Arg727_Ser783del).
  • the "positions_deleted" should contain two different positions, i.e. Cys76_Glu79, not Cys76_Cys76.
    • the "positions_deleted" should be listed from 5' to 3', i.e. Cys76_Glu79, not Glu79_Cys76.
  • for all descriptions, the most C-terminal position possible of the reference sequence is arbitrarily assigned to have been changed (3'rule).
  • a nonsense variant, a variant changing an amino acid to a translation termination (stop) codon, is described as a substitution (p.Trp26Ter or p.Trp26*; see Substitution). A nonsense variant is not described as a Deletion of the C-terminal end of the protein (e.g., p.Trp26_Arg1623del).
  • variants extending the amino acid sequence at the C-terminal end with one or more amino acids, are described as an Extension.
  • deletions on the DNA or RNA level that
    • introduce an immediate translation termination (stop) codon, are described as a nonsense variant.
    • encode an open reading frame which after the deleted sequence shifts to another reading frame, are described as a frameshift.

Examples#

one amino acid#

  • NP_003997.2:p.Val7del
    a deletion of amino acid Val7 in the reference sequence NP_003997.2.

  • NP_003997.2:p.(Val7del)
    the predicted consequence on the protein level is a deletion of amino acid Val7 in the reference sequence NP_003997.2.

  • NP_003997.2:p.Trp4del
    a deletion of amino acid Trp4 in the sequence MetLeuTrpTrpGlu to MetLeuTrpGlu.
    NOTE: for deletions in single amino acid stretches or tandem repeats, the most C-terminal residue is arbitrarily assigned to have been deleted.

several amino acids#

  • NP_003997.2:p.Lys23_Val25del
    a deletion of amino acids Lys23 to Val25 in reference sequence NP_003997.2.

  • NP_003997.2:p.(Pro458_Gly460del)
    a deletion of amino acids Pro458, Pro459, and Gly460 in reference sequence NP_003997.2.
    NOTE: the underlying DNA variant LRG_232t1:c.1365_1373del affects amino acids Pro455, Pro456, and Gly457, but the 3'rule needs to be applied.

one or more exons#

  • NP_003997.2:p.(His321_Glu383del)
    the predicted consequences of a deletion of exon 10 of the DMD gene, deleting amino acids His321 to Glu383 in reference sequence NP_003997.2.

  • NP_003997.2:p.(Asp90_Val120del)
    the predicted consequences of a deletion of exon 5 of the DMD gene, deleting amino acids Asp90 to Val120 in reference sequence NP_003997.2.
    NOTE: since the 3'rule needs to be applied, the description p.(Val89_Gln119del) is not correct.

  • NP_003997.2:p.(His321Leufs*3)
    the predicted consequences of a deletion of exons 10 to 11 of the DMD gene, creating a frameshift starting at amino acid His321, replacing it with Leu and terminating after three codons.

  • NP_003997.2:p.?
    the predicted consequences of a deletion of exons 1 to 2 of the DMD gene, deleting the translation initiation codon.
    NOTE: since exon 1 and the translation initiation codon are deleted, no reliable predictions can be made. Possibly, no transcript is generated and no protein (p.0?).

  • NP_003997.2:p.?
    the predicted consequences of a deletion of exons 74 to 79 of the DMD gene, deleting the translation termination codon.
    NOTE: since the last exon (exon 79) is deleted, it is not known what sequences after exon 73 are added to the transcript, and no reliable predictions can be made.

other examples#

  • p.Gly2_Met46del
    a deletion of amino acids Gly2 to Met46 as a consequence of a variant silencing translation initiation at Met1, but activating a new downstream translation initiation site (at Met46).
    NOTE: the 3' rule has been applied.

  • p.Trp26Ter (p.Trp26*)
    amino acid Trp26 is changed to a stop codon (Ter, *).
    NOTE: this change is by definition not described as a deletion of the C-terminal end of the protein (i.e. p.Trp26_Arg1623del).

  • NP_003997.1:p.Val7=/del
    a mosaic case where at amino acid position 7, besides the normal amino acid (a Val, described as Val7=), also protein is found containing a deletion (p.Val7del).
    NOTE: for the predicted consequences of a variant, the description is NP_003997.1:p.(Val7=/del).

Discussion#

Can I use p.Arg45del6 to describe a 6 amino acid deletion?

No, a deletion of more than one residue should mention the first and last residue deleted, separated using the range symbol (_, underscore), e.g., p.Arg45_Gly50del, and not p.Arg45del6.

Is the description of a deletion of exon 17 as p.EX17del still allowed?

A description like p.EX17del has never been allowed. Descriptions should be specific and indicate the amino acids affected by the change.

In literature I often see the description "deltaF508", "ΔF508"or "F508del" for a variant in the CFTR gene in patients with Cystic Fibrosis. Is this according to HGVS nomenclature a correct description?

No, the correct description of this variant is LRG_663t1:c.1521_1523del   r.(?)   p.(Phe508del). According to the HGVS nomenclature, all variants should be described at the most basic level, the DNA level. For protein studies, the variant can be described as NP_000483.3:p.Phe508del (NOTE: the protein reference sequence should be given).

What do you mean with "variants should be described on the protein level and not incorporate knowledge regarding the change on the DNA-level"?

It means that protein variant descriptions should be derived from comparing the variant protein sequence with the reference protein sequence. Knowledge on the underlying change on the DNA level should not be used. E.g., when MetTrpSerSerSerHisAsp.. changes to MetTrpSerSerHisAsp.., this is described as p.Ser5del. The information that on the DNA level the change is ..ATGTGGTCCAGTTCCCACGAT.. to ..ATGTGGTCCTCCCACGAT.., so the codon for Ser4 is deleted, is not used; the description p.Ser4del is not correct.