Nomenclature
Download pdf file of the current ISTH VWF SSC Guideline on VWF and its activities
The nomenclature for describing VWF and its activities is based on the most recent recommendations of the ISTH Scientific and Standardization Subcommittee on von Willebrand factor, as described by Mazurier and Rodeghiero, Thromb Haemost. 2001; 86: 712.
Recommended abbreviations for von Willebrand factor and its activities:
|
Attribute
|
Recommended Abbreviation
|
| Mature protein |
VWF |
| Antigen |
VWF:Ag |
| Ristocetin cofactor activity |
VWF:RCo |
| Collagen binding capacity |
VWF:CB |
| Factor VIII binding capacity |
VWF:FVIIIB |
Download pdf file of the current ISTH VWF SSC Guideline on VWF gene mutation and polymorphism nomenclature
The nomenclature for describing VWF gene mutations and polymorphisms and the classification of VWD mutations is based on the most recent recommendations of the ISTH Scientific Subcommittee on von Willebrand disease, as described by A.C. Goodeve et al, Thromb Haemost. 2001; 85(5): 929-31.
A series of papers on proposed mutation nomenclature schemes for human genes have
been published in Human Mutation produced by the "nomenclature working group", a
group of researchers representing interest in mutation detection from different fields of
research (1-3). Readers are recommended to refer to these publications, particularly to
that of Antonarakis et al (3) for further details of all circumstances where mutation
nomenclature is required. As several different numbering schemes have been used for
VWF in the past, authors are encouraged to indicate the scheme that is used.
At their first mention in a text, mutations may be described in detail, for example alanine
substituted by glycine at codon 123; insertion of a guanine following the adenine
nucleotide at position 1234. Thereafter, the nomenclature described below should be used.
cDNA sequence
The recommendation for the VWF cDNA is to continue to number from the A of the
initiator ATG site as +1. This numbering scheme results in nucleotide numbers 250 nt
lower than when numbering VWF from the transcription initiation site (4). The sequence
is available under accesion number NM_000552.
Gene DNA sequence
When the entire VWF genomic sequence becomes readily available, genomic DNA nt
numbering should start from the initiator ATG as +1, as for the cDNA. However, when
numbering, a lower case g for genomic DNA should be used in front of the nt number (eg
g.1234), to demonstrate which sequence is referred to. Numbering should be sequential
throughout the gene, from 1-178,000 as for the FIX gene (5). The exon or intron number
should also be given for orientation. Until the complete VWF gene sequence is readily
available, the partial VWF genomic sequence of Mancuso et al (6) may be used when
required.
Nucleotide changes
Nucleotide alterations should be referred to as indicated by examples in Table 1. The
original and mutated nucleotides are both given following the nucleotide position number,
to avoid confusion with amino acid numbering. Various symbols representing the nt
substitution can be utilised, such as G->A and G>A.
For insertion and deletion mutations, where one or two nt are involved, they should be
named. Where >2 nt are involved, only the number involved is required. For deletions or
insertions in repetitive sequence eg. AAAAAA, the most 3' nt number is arbitrarily
assigned.
For intronic changes, where nt close to the intron/exon boundary are numbered, it is
simple to use the cDNA numbering with a + or - sign to designate distance into the intron.
For alterations deeper into the intron, the full VWF genomic DNA sequence should be
used once it is readily available, until then, the sequence of Mancuso et al (6) may be
used. When using genomic VWF DNA sequence numbering to describe intronic sequence,
the intron number should also be given for orientation.
Changes in the upstream untranslated region are numbered from the A of the initiator
ATG (+1) as negative numbers.
|
Nucleotide change
|
Nomenclature example
|
Description
|
| Substitution |
1234G>A |
Guanine substituted by adenine at position 1234 in the VWF cDNA sequence |
| Substitution |
g1234G>A |
Guanine substituted by adenine at position 1234 in the complete VWF genomic sequence |
| Substitution |
5/1234G>A |
Guanine substituted by adenine at position 1234 in
block 5 of the partial VWF genomic sequence of Mancuso et al (7) |
| Deletion |
1234delG |
Deletion of guanine from position 1234 of the VWF cDNA sequence |
| Deletion |
1234delN |
N nt deleted at position 1234 in the VWF cDNA sequence, N >2 nt |
| Insertion |
1234insGT |
Insertion of guanine and thymidine after nt 1234 in the VWF cDNA sequence |
| Insertion |
1234insN |
N nt inserted after nt 1234 in the VWF cDNA sequence, N >2nt |
| Intronic change |
1234+1G>T |
Substitution of guanine of GT splice donor, 1st position of intron. Nt number 1234 is last nt of preceding exon of the VWF cDNA sequence |
| Intronic change |
1234-2A>G |
Substitution of adenine of AG splice acceptor, 2nd last position of intron. Nt 1234 is the first nt of the succeeding exon of the VWF cDNA sequence |
Table 1. Recommendations for VWF nucleotide alterations
Amino acid sequence
Numbering should start from the initiator methionine as the +1 position. Separate
numbering schemes for mature VWF should be discontinued, so avoiding confusion with
amino acid numbering in the propeptide. The use of single letter aa codes will facilitate
discrimination from the previous nomenclature, where the three letter amino acid codes
were widely used for aa in the mature VWF.
Amino acid alterations
Amino acid alterations should be referred to as indicated by examples in Table 2.
The wild type amino acid is given before the codon number and the mutant amino acid
following the number. This placement avoids confusion with the nucleotide numbering
scheme, where all nucleotides are given following the nucleotide position number.
Termination (stop) codons are designated by an X.
For insertion or deletion mutations, where one or two aa are involved, they should be
named. Where >2 aa are involved, only the number involved is required. For deletions or
insertions in repetitive sequence eg. LysLysLys, the most carboxyl (3') aa number is
arbitrarily assigned.
To facilitate comparison with earlier publications, at the first description in a manuscript
of a mutation in mature VWF, the previous nomenclature (for mature VWF, starting from
Ser764 of pre-pro VWF) should be given in parenthesis. For this purpose, the three letter
aa codes should be utilised.
|
Amino acid change
|
Nomenclature example
|
Description
|
| Missense |
R123G |
Arginine residue substituted by glycine at position 123 in the pre-pro VWF sequence |
| Nonsense |
R123X |
Arginine residue substituted by a stop codon at position 123 in the pre-pro VWF sequence |
| Insertion |
R123insS |
Insertion of a serine residue following the arginine residue at position 123 in the pre-pro VWF sequence |
| Deletion |
R123del |
Deletion of an arginine residue from position 123 in the pre-pro VWF sequence |
Table 2. Recommendations for VWF amino acid alterations
Polymorphisms
Polymorphic alterations should be referred to as indicated by examples in Table 3. Two
alleles which co-exist in the population at an arbitrarily designated polymorphic
frequency of >1% (7) and have no known deleterious effect on phenotype can be shown
at a specified location using a "/" symbol. The first allele shown should be that in the
reference sequence available on the VWF electronic database and the second the
polymorphic variant.
To avoid confusion, for polymorphic aa residues, the aa designations are given before the
codon position number, whereas for polymorphic nt, the nt designations are given
following the nt position number.
|
Polymorphic change
|
Nomenclature example
|
Description
|
| Single nucleotide polymorphism |
1234A/G |
Nucleotide 1234 in the VWF cDNA sequence is polymorphic. Two alleles known (adenine and guanine), that in reference sequence shown first |
| Insertion/deletion polymorphism |
1234C/delC |
Presence/absence of cytosine at position 1234 in the VWF cDNA sequence is polymorphic |
| Single amino acid polymorphism |
A/G1234 |
Amino acid residue at position 1234 in the pre-pro VWF sequence is polymorphic. Two alleles known (alanine and glycine), that in reference sequence shown first |
Table 3. Recommendations for VWF polymorphism nomenclature
Recommended Abbreviations for VWF and Its Activities
The nomenclature for describing VWF and its activities is based on the most recent recommendations of the ISTH Scientific Subcommittee on von Willebrand disease, as described by C.Mazurier and F.Rodeghiero (8).
|
Attribute
|
Recommended abbreviation
|
| Mature protein |
VWF |
| Antigen |
VWF:Ag |
| Ristocetin cofactor activity |
VWF:RCo |
| Collagen binding capacity |
VWF:CB |
| Factor VIII binding capacity |
VWF:FVIIIB |
| Factor VIII coagulant activity |
FVIII:C |
Table 4. Recommended abbreviations for VWF (and FVIII) and its activities
References
- Beaudet AL, Tsui L-C. A suggested nomenclature for designating mutations. Human
Mutation 1993; 2: 245-248.
- Ad Hoc Committee on Mutation Nomenclature. Update on nomenclature for human
gene mutations. Human Mutation 1996; 8: 197-202.
- Antonarakis SE, Nomenclature Working Group. Recommendations for a nomenclature
system for human gene mutations. Human Mutation 1998; 11: 1-3.
- Sadler JE. A revised classification of von Willebrand disease. Thromb Haemost 1994;
71:520-525.
- Yoshitake S, Schach BG, Foster DC, Davie EW, Kurachi K. Nucleotide-sequence of
the gene for human factor-IX (antihemophilic factor-B). Biochemistry 1985; 24:
3736-3750.
- Mancuso DJ, Tuley EA, Westfield LA, Worrall NK, Shelton-Inloes BB, Sorace JM,
Alevy YG, Sadler JE. Structure of the gene for human von Willebrand-factor. J Biol
Chem 1989; 264: 19514-19527.
- Peake I, Winship P. What is a polymorphism. Blood 1991; 78: 251.
- Mazurier C, Rodeghiero F. Recommended abbreviations for von Willebrand Factor and its activities. Thromb Haemost 2001; 86: 712.
Download pdf file of the current ISTH SSC VWF Nomenclature Guidelines
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