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.
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
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)
two variants separated by one or more nucleotides should be described individually and not as a “delins”
exception: two variants separated by one nucleotide, together affecting one amino acid, should be described as a “delins”
NOTE: the SVD-WG is preparing a proposal to modify this recommendation. To apply the current rule one needs to know whether the two variants are in a coding sequence and affecting one amino acid. Recommendations should be general. The new recommendation will be: two variants separated by less then two nucleotides should be described as a “delins”
inversions are not used on protein level. Depending on the (predicted) consequences of an inversion on protein level, changes are usually described as either a delins or a frame shift.
inversion of nucleotides g.32361330 to g.32361333, changing ..CATCAGCCT.. to ..CACTGACCT..
inversion of nucleotides c.5657 to c.5660 (coding DNA reference sequence), changing ..AGGCTGATG.. to ..AGGTCAGTG..
inversion of the 16 nucleotides from position c.4145 to c.4160
a large inversion (212,434 nucleotides) from position g.111754331 to g.111966764
a copy of nucleotides c.850 to c.900 is inserted, in inverted orientation, 5’ of the original sequence, between nucleotide c.849 and c.850
a copy of nucleotides c.850 to c.900 is inserted, in inverted orientation, 3’ of the original sequence, between nucleotide c.900 and c.901
an inverted copy of nucleotides c.851 to c.940, with a G>A substitution of nucleotide c.884, is inserted directly 3’ of the original sequence
an inverted copy of nucleotides c.851 to c.940, with a deletion from nucleotides c.886 to c.902, is inserted directly 3’ of the original sequence
Is the change AAGC to TTCG an inversion?
No, an inversion would change AAGC to GCTT, its reverse-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 reverse-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).