EAHAD DBs Latest: Mar 2022 - F7 Database Updated to 2021
See Citing Us (below) for information on our recent papers on the EAHAD DBs.
During 2019 over 4500 additional cases were added to the EAHAD F8 database, including over 1000 new unique variants. There are currently
3052
unique variants in the F8 gene compiled within this database corresponding to
10144
individual cases.
F8 Gene Variants
Haemophilia A is caused by variants in the gene F8 that codes for coagulation factor VIII. F8 gene inversions (in c.50% of severe cases) are not listed in this database.
What can you do in this database ?
You can search for variants reported in the F8 gene.
You can look in the database for sequence, structural and statistical information on the gene variants. You can also submit new mutations/variants to EAHAD and thus contribute to the genetic services provided through this database.
F8 Variants at Leiden Open Variant Database (LOVD)
The basic F8 case data in this DB are mirrored at LOVD:
F8 at LOVD.
Simple Amino Acid Search
Exon and Intron based search
Reference Sequences and Nomenclature (HGVS and Legacy)
The reference sequence used for FVIII protein is NP_000123.1 and its corresponding stable Locus Reference Genomic DNA sequence (LRG) is LRG_555. Codons and amino-acids are numbered on this site in two ways. In HGVS numbering, codons are numbered with codon +1 coding for the first residue (Met) of the 19-residue signal peptide (this is -19 in Legacy numbering). In Legacy numbering, codon +1 refers to that coding for the first amino-acid of the mature FVIII protein (in HGVS numbering, this is codon +20). HGVS numbering is recommended, however Legacy numbering is extensively used in FVIII publications, particularly before the year 2000.
Classification of Variant Phenotype
Variants causing haemophilia A are classified by factor VIII clotting activity level into the following groups: severe (≤1%), moderate (1-5%) and mild >5%. Where a laboratory value does not correlate with the severity given in a particular report we have attempted to clarify the discrepancy with the original authors. If the discrepancy remains, the clinical severity of the phenotype as reported by the authors has been used. Note that the reported level may reflect a trough level rather than the true baseline in patients on prophylaxis. This may explain why a variant that should result in a null allele is associated with detectable factor VIII activity or antigen. For variants causing mild haemophilia A we have attempted to indicate whether the deleterious effect of the mutation is predominantly quantitative (reduced levels of a normally functioning protein) or qualitative (dysfunctional protein which may or may not also be associated with a reduction in protein level). This is indicated in results tables under the "Type" heading using the conventions used for other coagulation proteins so that Type I refers to quantitative defects with an activity:antigen ratio >0.7 and Type II are qualitative defects with a ratio ≤ 0.7. These categories broadly correspond respectively to the terms CRM (cross-reacting material) negative and positive sometimes found in older publications.
Have you or someone you know been diagnosed with haemophilia A?
The information contained on this web site is provided for scientific research purposes only. We do not give medical advice or recommend any particular treatment for specific individuals. Click
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Acknowledgements
This work was supported through a medical educational grant from Pfizer UK Ltd.
We thank the Special Trustees of the Royal Free Hospital and the Katharine Dormandy Trust for Haemophilia and Related Disorders for their support.
We thank the European Association for Haemophilia and Allied Disorders (EAHAD) for supporting our work.
We thank the Medical Research Council for their supporting the Database from 1987 to 2010.
The following people worked on this project:
Pavithra M Rallapalli, formerly of UCL, London
Geoffrey Kemball-Cook, The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London
Edward G. Tuddenham, The Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Royal Free Hospital, London
Recent publication on the EAHAD Coagulation Factor Databases:
The European Association for Haemophilia and Allied Disorders (EAHAD) Coagulation Factor Variant Databases: Important resources for haemostasis clinicians and researchers.
McVey JH, Rallapalli PM, Kemball-Cook G, Hampshire DJ, Giansily-Blaizot M, Gomez K, Perkins SJ, Ludlam CA.
Access here: Haemophilia. 2020 Mar;26(2):306-313. doi: 10.1111/hae.13947.
Latest Release- Version 3.1 (December 2020)
This website is under development. For all comments, queries or suggestions please contact f8@eahad-db.org.
The information contained on this web site is provided for research purposes only. All information and content on this web site are protected by copyright. All rights are reserved.