Mutation nomenclatures

The genomic reference sequence used for annotating TP53 mutations from R17 release is NC_000017.10 (hg19 build) from GenBank.

To report mutations, please follow the recommendations provided by HGVS.

You can also check Mutalyzer, a tool that help you to format your mutation data according to HGVS guidelines and to convert positions between different build and isoforms.

Here is the basis of numbering:

  • coding region G to C substitution of nt 303, i.e. nt 3 of the coding region (cDNA)
  • genomic Reference Sequence cDNA Reference Sequence
    g.303G>C c.3G>C
  • intron (regarding the numbering of intronic nucleotides, see Description of intronic variants)  -  T to G substitution of the second nt in the intron (88+2) positioned between cDNA nts 88 and 89 (intron 2)
  • genomic Reference Sequence cDNA Reference Sequence
    g.490T>G c.88+2T>G
      -  G to T substitution of the last nt of the intron  (89-1) positioned between cDNA nts 88 and 89 (intron 2)
    genomic Reference Sequence cDNA Reference Sequence
    g.688G>T c.89-1G>T
  • alternatively spliced exon (coding DNA reference sequence used should represent the major and largest transcript of the gene) - G to C substitution of intronic nt 812 (cDNA 123+89)
  • genomic Reference Sequence cDNA Reference Sequence
    g.812C>T c.123+89C>T

    Here are some examples:

    Type of change DNA
    (examples shown relate a to cDNA reference sequence)
    RNA
    (report only when RNA was analyzed)
    Protein
    (NOTE, change deduced only!)
    substitution c.3G>T

    c.88+2T>G

    c.89-1G>T

    NM_004006.1:c.3G>T

    GJB6:c.3G>T
    r.67g>u p.Trp26Cys
    (p.W26C)

    p.Trp26X
    (p.W26X)
    deletion c.13del
    (c.13delT)

    c.13_16del   (c.13_16del4)

    c.120_123+4del8

    c.13-?_300+?
     r.13del
    (r.13delu)

    r.13_16del   (r.13_16del4)

    -

    r.13_300del
    p.Gly4del
     (p.G4del)

    p.Gly4_Gln6del
    (p.G4_Q6del) 
    duplication  c.13dup
    (c.13dupT)

    c.92_94dup   
    (c.92_94dupGAC) 
    r.13dup   (r.13dupu)

    r.92_94dup   
    (r.92_94dupgac) 
    p.Gly4dup
    (p.G4dup)

    p.Gly4_Gln6dup
    ( p.G4_Q6dup)
    insertion  c.51_52insT

    c.51_52insGAGA
    r.51_52insu

    r.51_52insgaga
    p.Lys2_Leu3insGlnSer
    (p.K2_L3insQS)
    inversion c.77_80inv r.77_80inv p.Gly4_Gln6inv (p.G3_Q6inv)
    complex c.112_117delinsTG
    (c.112_117del6insTG)
    r.112_117delinsug
    (r.112_117del6insug)
    p.Cys28_Lys29delinsTrp
    (p.C28_K29delinsW)
    two changes in one allele c.[76C>T;83G>C] r.[76C>T;83G>C]  p.[Trp13X;Pro43Ala] 
    recessive disease (changes in different alleles) c.[76C>T]+[87G>A]

    c.[76C>T]+[?]

    c.[76C>T]+[=]
    r.[76c>u]+[87g>a]

    r.[76c>u]+[?]

    r.[76c>u]+[=]
    p.[Trp13X]+[Cys28Arg]

    p.[Trp13X]+[?]

    p.[Trp13X]+[=]
    recessive disease (changes in different genes) (GJB2:c.[76C>T]+GJB6:c.[87G>A]) (GJB2:r.[76c>u]+
    GJB6:r.[87g>a])
    GJB2:p.[Trp13X]+
    GJB6:p.[Cys28Arg]
    frame shift
    (protein only)
    - - p.Arg97ProfsX23
    (p.Arg97fs)