DNA Recommendations

Inversion Variant


Definitions

Inversion
a sequence change where, compared to a reference sequence, more than one nucleotide replacing the original sequence are the reverse complement of the original sequence.

Description

Format: “prefix”“positions_inverted”“inv”, e.g. g.123_345inv

“prefix” = reference sequence used = g.
“positions_inverted” = range of nucleotides inverted = 123_345
“inv” = type of change is an inversion = inv


Note

  • prefix reference sequences accepted are g., m., c. and n. (genomic, mitochondrial, coding DNA and non-coding DNA)
  • by definition, the region inverted (“positions_inverted”) contains more then one nucleotide. The description g.234inv is therefore not allowed; a one nucleotide inversion should be described as a substitution
  • for all descriptions the most 3’ position possible of the reference sequence is arbitrarily assigned to have been changed (3’rule)
    • the 3’rule applies to ALL descriptions (genome, gene, transcript and protein) of a given variant
  • inverted duplications are described as an insertion using the format g.234_235ins123_234inv, not as g.123_456dupinv (see Q&A)
  • under discussion, see Proposal for complex variants
    { } (curly braces) can be used to list any change in the inverted sequence (“positions_inverted”) which is different when compared to the source, e.g. g.123_345inv{233A>G}
  • inversions are not used on Protein level

Examples

  • g.1077_1080inv
    inversion of nucleotides g.1077 to g.1080, changing ..AGGCTGATT.. to ..AGGTCAGTT..
  • c.77_80inv
    inversion of nucleotides c.77 to c.80 (coding DNA reference sequence), changing ..AGGCTGATT.. to ..AGGTCAGTT..
  • g.203_506inv
    inversion of the 304 nucleotides from position g.203 to g.506
  • g.111754331_111966764inv
    a large inversion (212,434 nucleotides) from position g.111754331 to g.111966764
  • g.122_123ins123_234inv
    a copy of nucleotides g.123 to g.234 is inserted, in inverted orientation, 5’ of the original sequence, between nucleotide g.122 and g.123
  • g.234_235ins123_234inv
    a copy of nucleotides g.123 to g.234 is inserted, in inverted orientation, 3’ of the original sequence, between nucleotide g.234 and g.235
  • g.122_123ins213_234invinsAins123_211inv
    an inverted copy of nucleotides g.123 to g.234, with a G>A substitution of nucleotide g.212, is inserted directly 3’ of the original sequence
  • g.122_123ins212_234inv123_199inv
    an inverted copy of nucleotides g.123 to g.234, with a deletion from nucleotides g.200 to g.211, is inserted directly 3’ of the original sequence

Q&A

Is the change AAGC to TTCG an inversion?

No, an inversion would change AAGC to GCTT, its revese-complement. TTCG is only the complement of AAGC.

Is the change AAGC to CGAA an inversion?

No, an inversion would change AAGC to GCTT, its revese-complement. CGAA is only the reverse of AAGC.

Is it not better to describe the variant g.234_235ins123_234inv as g.123_234dupinv?

The descriptions of duplications is regularly debated "Why not remove the variant type "duplication" and describe all dups as "insertion", it will make the HGVS rules in total simpler. While we can not do this for historic reasons (duplications are in use since the beginning), we will restrict the use of "dup" as much as possible. Regarding a "dupinv" one could argue that an "inverted copy" is not "a copy inserted directly 3' of the original copy" and thus by definition this variant is not a duplication but an "insertion". Therefore the recommendation is to describe inverted duplication using the format g.122_123ins123_234inv or g.234_235ins123_234inv depending on whether the inverted copy is 5' or 3' of the original copy (reference sequence).