DNA Recommendations

Repeated sequences Variant


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.


Format (unique repeat): “prefix”“position_first_nucleotide_first_repeat_unit”“repeat_sequence”[“copy_number”], e.g. g.123CAG[16]

  • “prefix” = reference sequence used = g.
  • “position_first_nucleotide_first_repeat_unit” = first nucleotide of first repeat unit = 123
  • “repeat_sequence” = sequence repeat unit = CAG
  • [ = opening symbol for copy number allele = [
  • “copy_number” = number of repeat units = 16
  • ] = closing symbol for copy number allele = ]

Format (mixed repeat): “prefix”“range_repeated_sequence”“repeat_sequence_unit1”[“copy_number”]”repeat_sequence_unit2”[“copy_number”], e.g. g.123_191CAG[19]CAA[4]

  • “prefix” = reference sequence used = g.
  • “range_repeated_sequence” = position first to last nucleotide repeated sequence (range) = 123_191
  • “repeat_sequence_unit1” = sequence first repeat unit = CAG
  • [ = opening symbol for allele = [
  • “copy_number” = number of repeat units = 19
  • ] = closing symbol for allele = ]
  • “repeat_sequence_unit2” = sequence first repeat unit = CAA
  • [ = opening symbol for allele = [
  • “copy_number” = number of repeat units = 4
  • ] = closing symbol for allele = ]


  • reference sequences accepted are g., m., c. and n. (genomic, mitochondrial, coding DNA and non-coding DNA)
    • NOTE: in the protein coding region repeat descriptions are 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:c.2692_2693dup and not NM_024312.4:c.2686A[10], use NM_024312.4:c.1741_1742insTATATATA and not NM_024312.4:c.1738TA[6].
  • for mixed repeats the range of the reapeat sequence is given followed by a listing of each repeat unit and the copy number of each unit; NC_000012.11:g.112036755_112036823CTG[9]TTG[1]CTG[13].
  • NM_002111.6:c.54GCA[23] describes a repeated sequence, containing 23 GCA units (sequenced), NM_002111.6:c.54_110(GCA)[23] describes a repeated sequence, located from position c.54 to c.110, of 23 units which was not sequenced (so could be interrupted with other repeat units (e.g. ACA).


  • unique repeat
    • sequenced
      • NC_000014.8:g.101179660TG[14]
        a repeated TG di-nucleotide sequence starting at position g.101179660 on human chromosome 14, with 14 TG copies
      • NC_000014.8:g.101179660TG[14];[18]
        a repeated TG di-nucleotide sequence starting at position g.101179660 on human chromosome 14, is present with 14 TG copies on one allele and 18 TG copies on the other allele
    • repeat expansion disorders
      • unique repeat reference sequence
        • NM_023035.2(CACNA1A):c.6955CAG[26] (or c.6955_6993dup)
          a repeated CAG tri-nucleotide sequence starting at position c.6955 in the CACNA1A gene with 26 CAG copies (p.(Gln2319[26] or p.(Gln2319_Gln2331dup))
          NOTE: when not sequenced but estimated from fragment size the description is NM_023035.2(CACNA1A):c.(6928_7020)ins(39), i.e. indicating that at an unknown position between nucleotides c.6928 and c.7020 (the nucleotides amplified) there is an estimated insertion of 39 nucleotides
        • HD repeat
          in literature the Huntington’s Disease tri-nucleotide repeat, encoding a poly-Gln repeat on protein level, is known as the CAG repeat. However, based on the HTT (huntingtin) coding DNA reference sequence (GenBank LRG_763t1 or NM_002111.8) and applying the 3’rule, the repeat has to be described as an GCA repeat
          • LRG_763t1:c.54GCA[23]
            a sequenced GCA tri-nucleotide repeat starting at position c.54 contains 23 units, on protein level described as NP_002102.4:p.(Gln18)[25]
            NOTE: the GCA repeat is followed by ACAG extending the encoded Gln-repeat by 2)
  • mixed repeat reference sequence
    • repeat expansion disorders
      • HD repeat
        the allele sequenced from position c.54 to c.149 contains 23 GCA, 1 ACA, 2 GCC, 1 ACC and 10 GCC repeats
      • FMR1 repeat
        in literature the Fragile-X tri-nucleotide repeat is described as a CGG-repeat. However, based on a coding DNA reference sequence (GenBank NM_002024.5) and applying the 3’rule, the repeat has to be described as a mixed GGC-GGA-GGC repeat
        • NM_002024.5:c.-128_-69GGC[10]GGA[1]GGC[9]GGA[1]GGC[10]
          a sequenced GGC tri-nucleotide repeat from position c.-128 to c.-69 containing contains 10 GGC, 1 GGA, 9 GGC, 1 GGA and 10 GGC units (31 repeat units)
        • NM_002024.5:c.-129CGG[79]
          a repeated CGG tri-nucleotide sequence starting at position c.-129 with 79 CAG copies
          NOTE: by definition, since the reference sequence contains a mixed repeat (CGG and AGG units), the variant description only covers the sequence up to the first AGG interruption (position c.-99). A better description is NM_002024.5:c.-128_-69GGC[79]GGA[1]GGC[10]
        • NM_002024.5:c.-128GGM[108]
          a repeated mixed tri-nucleotide sequence starting at position c.-129 with 108 GGC/GGA copies
        • NM_002024.5:c.(-231_-20)ins(1800_2400)
          the amplified region containing the FMR1 repeat region (between nucleotides c.-231 and c.-20) contains an insertion of 1800 to 2400 nucleotides (600 to 800 GGC/GGA units)
      • CFTR intron 9
        the mixed repeat sequence form position c.1210-33 to c.1210-6 contains 11 GT and 6 T copies
        NOTE: when only the variable T-stretch is described the format is NM_000492.3:c.1210-12T[7] (see Q&A below)
    • NC_000012.11:g.112036755_112036823CTG[9]TTG[1]CTG[13]
      a complex repeated sequence from position g.112036755 to g.112036823 on chromosome 12 with first a CTG unit present in 9 copies, then a TTG unit present in 1 copy and then a CTG unit present in 13 copies
  • differing genomic (g.) and coding DNA (c.) descriptions
    NC_000001.10:g.57832719ATAAA[15] and NM_021080.3:c.-136-75952ATTTT[15] describe the same repeat allele in intron 3 of the DAB1 gene
    NOTE: based on the 3’ rule and the transcriptional orientation of the gene (minus strand) the description of the repeat units differs


Intron 9 of the CFTR gene ends with the sequence ...tgtgtgtgtgtttttttaacag[exon_10]. Both the TG and T stretches are variable in length (from 9 to 13 and 5 to 9 resp.). The reference sequence has 11 TG copies and 7 T's. Is it correct to describe an allele as c.1210-14TG[13]T[5] or for the T stretch as c.1210-6T[5]?

A complex case. First note that by applying the 3'rule it is a variable GT and not TG stretch. When the coding DNA reference sequence has TG11 followed by T7, the reference allele is described as c.1210-33_1210-6GT[11]T[6]. When only variability of the T-stretch is reported, the reference allele is described as c.1210-12T[7].
To indicate the overall variability found in the population the description is c.1210-33_1210-6GT[9_13]T[4_8] for the combined repeat and c.1210-12T[5_9] for the T-stretch.