About the mutations numbering
The numbering used follows the most recent recommendations of the ISTH Scientific Subcommittee on von Willebrand disease described by Goodeve et al. It is the same used in the international database of mutations in von Willebrand Disease (ISTH SSC VWF Database) in order to facilitate comparison between both and with other publications.
The VWF cDNA sequence numbering starts at the first adenine (A) of the original translation codon (ATG) being the position number +1. Using this rule, the initial transcription point is located 250 nt before the position +1. It means that the transcription starts in the position -250 nt. The sequence is available under accession number NM_000552.
From a given nucleotide is possible to calculate the affected residue applying the formula:
Integer [(number of nucleotide / 3) -250]
About the symbols in the family trees
See this schema...
About the equivalence letters > symptoms in clinical tables
A: Easy bruising
C: Bleeding from minor wounds
E: Postoperative bleeding
F: Bleeding after dental procedure
H: Oral cavity bleeding
I: Gastrointestinal bleeding
J: Postpartum hemorrhage
K: Muscle hematomas
L: Central nervous system bleeding
|According to: J. Thromb. Haemost. 2006; 4:766-773.|
About the mutations nomenclature
There must be considered the following nomenclature parameters to find and consult the specific mutations in the genes:
The substitutions start with the number of the affected nucleotide followed by the change produced. 1093C>T denotes that, in the nucleotide number 1093 of the sequence, the C is replaced by a T
Deletions are indicated with a del after the nucleotide number. 2157delA denotes the deletion of an A in the position 2157 of the reference sequence.
Insertions are indicated with an ins after the nucleotide number. 893insG denotes the insertion of a G after the position 893 of the reference sequence.
Mutations in introns, when the complete genomic sequence is not known, is denoted by the number of intron (IVS) and positive numbers numbering from the G of the donor splice site GT or negative numbers from the G of the acceptor splice site AG. IVS62+1G>A indicates the G to A substitution at the nucleotide +1 of intron 62. IVS4-2A>C denotes the replacement of A to C at nucleotide -2 of intron 4. When you know the complete genomic sequence of the gene, the mutation is indicated by the number of nucleotide sequence of the reference.
For amino acids nomenclature, the format is R782Q (arginine at codon 782 replaced by glutamine). The amino acid "wild type" is indicated before the number of codon and the mutant amino acid on the post. In some cases, the mutation also can be shown as Arg782Gln.
Stop codons are indicated by X. For example R365X indicates that the arginine at position 365 is replaced by a stop codon.
Nomenclature for the description of human sequence variations
Hum Genet. 2001 Jul;109(1):121-4.
Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion
Hum Mutat. 2000;15(1):7-12.