UniProtKB/Swiss-Prot P04275: Variant p.Arg1306Trp

von Willebrand factor
Gene: VWF
Chromosomal location: 12p13.2-p13.3
Variant information

Variant position:  1306
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Tryptophan (W) at position 1306 (R1306W, p.Arg1306Trp).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from large size and basic (R) to large size and aromatic (W)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In VWD2.
Any additional useful information about the variant.



Sequence information

Variant position:  1306
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2813
The length of the canonical sequence.

Location on the sequence:   SRLSEAEFEVLKAFVVDMME  R LRISQKWVRVAVVEYHDGSH
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         SRLSEAEFEVLKAFVVDMMERLRISQKWVRVAVVEYHDGSH

Mouse                         SMLSEAEFEVLKAFVVGMMERLHISQKRIRVAVVEYHDGSR

Dog                           SKLSEDEFEVLKVFVVGMMEHLHISQKRIRVAVVEYHDGSH

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 764 – 2813 von Willebrand factor
Domain 1277 – 1453 VWFA 1; binding site for platelet glycoprotein Ib
Disulfide bond 1272 – 1458
Alternative sequence 315 – 2813 Missing. In isoform 2.


Literature citations

Molecular basis of von Willebrand disease type IIB. Candidate mutations cluster in one disulfide loop between proposed platelet glycoprotein Ib binding sequences.
Randi A.M.; Rabinowitz I.; Mancuso D.J.; Mannucci P.M.; Sadler J.E.;
J. Clin. Invest. 87:1220-1226(1991)
Cited for: VARIANTS VWD2 TRP-1306; CYS-1308 AND PRO-1613;

The molecular defect in type IIB von Willebrand disease. Identification of four potential missense mutations within the putative GpIb binding domain.
Cooney K.A.; Nichols W.C.; Bruck M.E.; Bahou W.F.; Shapiro A.D.; Bowie E.J.W.; Gralnick H.R.; Ginsburg D.;
J. Clin. Invest. 87:1227-1233(1991)
Cited for: VARIANTS VWD2 TRP-1306; CYS-1308; MET-1316 AND GLN-1341; VARIANT HIS-1399;

Molecular study of von Willebrand disease: identification of potential mutations in patients with type IIA and type IIB.
Pietu G.; Ribba A.S.; de Paillette L.; Cherel G.; Lavergne J.-M.; Bahnak B.R.; Meyer D.;
Blood Coagul. Fibrinolysis 3:415-421(1992)
Cited for: VARIANTS VWD2 TRP-1306; MET-1316; THR-1628 AND SER-1648;

Type IIB von Willebrand's disease: gene mutations and clinical presentation in nine families from Denmark, Germany and Sweden.
Donner M.; Kristoffersson A.-C.; Lenk H.; Scheibel E.; Dahlback B.; Nilsson I.M.; Holmberg L.;
Br. J. Haematol. 82:58-65(1992)
Cited for: VARIANTS VWD2 TRP-1306; CYS-1308; LEU-1314 AND LEU-1318;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.