Skip to content

Repeated Sequences#

Repeated sequence: a sequence where, compared to a reference sequence, a segment of one or more nucleotides (the repeat unit) is present several times, one after the other.

Syntax#

NOTE: a Community Consultation proposal is being prepared which will suggest to allow only the format where the entire range of the repeated sequence is indicated; so r.123_191cag[23], not r.123cag[23].

Positions only
Syntax sequence_identifier ":r." positions "[" copy_number "]"
Examples
  • NM_004006.3:r.9495_9497[4]
  • NM_004006.3:r.-110_-108[6]
Sequence given
Syntax sequence_identifier ":r." start_position sequence "[" copy_number "]"
Examples
  • NM_004006.3:r.9495caa[4]
  • NM_004006.3:r.-110gcu[6]
Explanation of Symbols
  • coordinate_type: the coordinate type, indicating the type of numbering used; r
  • copy_number: the observed number of repeats
  • positions: the range of nucleotides of the first repeat unit; 9495_9497
  • sequence: the RNA sequence of one repeat unit; caa
  • sequence_identifier: the sequence identifier used; NM_004006.3
  • start_position: the position of the first nucleotide of the repeat; 9495
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.
  • repeated sequences include both small (mono-, di-, tri-, etc., nucleotide) and larger (kilobase-sized) repeats.
  • the format based on repeat position is preferred, descriptions of the repeat sequence quickly become too lengthy.
    NOTE: while r.123cug[23] describes a repeat of 23 cug units, r.123_125[23] describes a tri-nucleotide repeat of 23 units which could be interrupted with other units (e.g., a rare cua). The description r.123cug[23] can thus only be used when the repeat was sequenced.
  • the format r.-125_-123cug[4] should not be used; it contains redundant information (-125_-123 and cug).
  • for composite repeats, the basic format can be used, successively listing each different repeat unit; r.456_465[4]466_489[9]490_499[3].
  • exception: using a coding RNA reference sequence, a repeated sequence variant description can be used only for repeat units with a length which is a multiple of 3, i.e. which can not affect the reading frame. Consequently, use NM_024312.4:r.2692_2693dup and not NM_024312.4:r.2686a[10]; use NM_024312.4:r.1741_1742insuauauaua and not NM_024312.4:r.1738ua[6]. This restriction only applies to the coding sequence, which does not include the UTR sequence. As such, NM_024312.4:r.-6_-3g[6] is valid as the reading frame is not affected.

Examples#

  • r.-124_-123[14] (alternatively r.-124ug[14])
    a repeated di-nucleotide sequence, with the first unit located from position r.-124 to r.-123, is present in 14 copies.
    NOTE: when the repeat is variable in the population and the reference sequence has 15 units, the description r.-123ug[14] is preferred over r.-97_-96del.
    NOTE: when the repeat is variable in the population and the reference sequence has 15 units, the description r.-123ug[17] is preferred over r.-99_-96dup.

  • r.-124_-123[14];[18] (alternatively r.-124ug[14];[18])
    a repeated di-nucleotide sequence, with the first unit located from position r.-124 to r.-123, is present in 14 copies on one allele and 18 copies on the other allele.

  • FMR1 GGC-repeat: in literature, the Fragile-X tri-nucleotide repeat is known as the CGG-repeat. However, based on a coding RNA reference sequence (GenBank NM_002024.5) and applying the 3'rule, on the RNA level, the repeat has to be described as a ggc-repeat (see Recommendations).

    • r.-128_-126[79]
      an extended repeat of exactly 79 units.
      NOTE: r.-128ggc[79] can only be used when the repeat has been sequenced, excluding it is interrupted by one or more gga-triplets.

    • r.-128_-126[(600_800)]
      the repeated tri-nucleotide sequence, starting at position c.-128, has an estimated size of between 600 and 800 copies.
      NOTE: the repeat can be pure or a mix of ggc and gga triplets.

  • HD AGC-repeat: based on the HTT (huntingtin) coding DNA reference sequence (GenBank NM_002111.6), applying the 3'rule, on the RNA level, the Huntington's Disease tri-nucleotide repeat is described as an agc (not cag) repeat.

    • r.53agc[19]
      NOTE: the coding RNA reference sequence (NM_002111.6) contains an allele of 21 agc repeats.
      NOTE: on protein level, the reference allele contains 21 Glns, described as p.Gln[21] (alternatively p.Q[21]). The difference derives from the fact that the agc repeat is interrupted by a aac-triplet (caa coding) at position 20.

    • r.53_55[31]
      the coding RNA reference sequence (NM_002111.6) contains a tri-nucleotide allele of 32 repeats (agc-19, aac, agc, cgc, cac, cgc-7, cuc-2) encoding 21 Gln and 11 Pro-residues.