Listing of all reported Polymorphisms in the FVIII Gene 
08-May-12
Polymorphic nucleotide substitutions found in the factor VIII gene of normal subjects or patients with haemophilia A. 
NOTE: THERE WAS A VERY IMPORTANT PAPER ON FVIII POLYMORPHISMS PUBLISHED IN MAY 2007
Viel et al, (2007) Blood 109, 3713-3724. Please consult this for important updates on FVIII polymorphisms.
Material from this paper has not been added to the listings below, which is maintained in its pre-2007 state.
The initial version of this listing was compiled by Dr Anne Goodeve at the Division of Genomic Medicine, University of Sheffield. 
Notes:
Southern: Southern blotting; PCR: polymerase chain reaction; ASO: allele-specific oligonucleotide hybridisation
Nucleotide number and codon number after Gitschier et al (1994)
Alleles: for diallelic polymorphisms, the most common allele is listed first. Alleles are referred to by either size of observed DNA fragments in kb, whether a restriction enzyme cuts (+) or does not (-), or the allelic DNA sequence.
Frequency: ?, no frequency data available. All frequencies are for Caucasian populations, unless shown by * (these latter are for Oriental (Chinese or Japanese) populations.
1. Intronic Polymorphisms
Detection By: Exon/Intron Location Sequence Alleles Frequency References Date added to HADB
Southern/TaqI 5' flanking 17kb 5' - 9.5/4.0 0.72/0.28 Kenwrick et al (1991) Dec-91
MPCR-CSGE IVS3  (+7) insT - - absent in at least 50 HA X chrs Jayandharan et al (2005) Aug-07
MPCR-CSGE IVS5 (-23) delC - - absent in at least 50 HA X chrs Jayandharan et al (2005) Aug-07
MPCR-CSGE IVS5 (-42) delC - - absent in at least 50 HA X chrs Jayandharan et al (2005) Aug-07
PCR/ASO IVS 7, nt27 - - A/G 0.52/0.48 Kogan & Gitschier(1990) Dec-90
direct sequencing IVS 7, nt32 - - G>C ? Klopp et al (2002) Dec-02
direct sequencing IVS 7, nt32 - - G>C ? Klopp et al (2002) Dec-02
MPCR-CSGE IVS9 (+18) T>G - - absent in at least 50 HA X chrs Jayandharan et al (2005) Aug-07
PCR/(CA)n repeat IVS 13 - - >10 25(0); 24(0.013); 23(0.05); 22(0.11); 21(0.29); 20(0.45); 19(0.07); 18(0.006); 17(0); 16(0.006) Lalloz et al (1991) Dec-91
? IVS 14 cDNA 5219+3 - - A/G ? Higuchi et al (1990) Dec-90
PCR/BclI IVS 18 - - T+/A- 0.71/0.29 Kogan et al (1987) Dec-87
PCR/HindIII IVS 19, nt 103 - - -/+ 0.75/0.25 Graham et al (1990) Dec-90
PCR/(GT)n(AG)n repeat IVS 22 - - >6 28(0.013); 27(0); 26(0.667); 25(0.307); 24(0); 23(0.013); Lalloz et al (1994) Dec-94
Southern/XbaI IVS 22 - - 4.8/6.2 0.59/0.41 Wion et al (1986) Dec-86
Southern/MspI IVS 22 - - 3.8/4.0 0.65/0.35* Inaba et al (1990) Dec-90
Southern/BglI IVS 25 - - 5.0/20.0 0.90/0.10 Antonarakis et al (1985) Dec-85
Southern/MspI 3' flanking - - 7.5/4.3+3.2 0.68/0.32 Youssoufian et al (1987) Dec-87
2. Exonic Polymorphisms
Please note that aminoacid numbering given below is for the mature processed protein, as used almost universally in FVIII studies.       
To convert to HGVS-type aminoacid numbering (where initiator Met =+1) add 19 to aminoacid numbers.         
Exon/Intron Nucleotide No. Codon Nucleotide Change Aminoacid Change FVIII:C (%) FVIII:Ag (%) Alleles Frequency Comments References Date added to HADB
1 102 15 GAC GAT Asp Asp ? ? C/T ? - Higuchi et al (1990) Dec-90
2 224 56 GAT GTT Asp Val ? ? A/T ? - Toole et al (1984); Lin et al (1993) Dec-93
7 ? 285 TCC TCT Ser Ser <1 ? C/T ? also has missense V234F Freson et al (1998) Apr-99
8 ? 343 GCG GCA Ala Ala <1 <1 G/A ? also has Intron 22 Inv Pieneman et al (1995) Jun-96
8 ? 343 GCG GCA Ala Ala 27 ? G/A ? carrier female also has A296T d'Oiron et al (2000) Aug-01
10 1508 484 CGT CAT Arg His 1 ? G/A ? also has causative Glu122->Lys Theophilus et al (2001) Aug-01
12 1866 603 CTT CTC Leu Leu ? ? T/C ? - Antonarakis et al (unpub) Dec-91
14 3376 1107 AGG TGG Arg Trp <1 ? T/C absent in at least 50 HA X chrs also has IVS1 inversion Jayandharan et al (2005) Aug-07
14 3376 1107 AGG TGG Arg Trp <1 ? T/C absent in at least 50 HA X chrs also has R1966Stop Jayandharan et al (2005) Aug-07
14 3780 1241 GAC GAG Asp Glu ? ? C/G ?; 0.73/0.27; 0.988/0.012* - Gitschier et al (1984); Higuchi et al (1991b); Lin et al (1993) Dec-91
14 3780 1241 GAC GAG Asp Glu ? ? C>G ? mild, no other mutation found Klopp et al (2002) Dec-02
14 3780 1241 GAC GAG Asp Glu ? ? C>G ? severe, no other mutation found Klopp et al (2002) Dec-02
14 3780 1241 GAC GAG Asp Glu ? ? C>G ? severe, also has Y813X Klopp et al (2002) Dec-02
14 3780 1241 GAC GAG Asp Glu ? ? C>G ? severe, also has IVS22 inversion Becker et al (1996) Aug-96
14 3780 1241 GAC GAG Asp Glu ? ? C>G ? moderate, no other mutation found Fernandez-Lopez et al (2005) Jul-07
14 3780 1241 GAC GAG Asp Glu ? ? C>G ? moderate, no other mutation found Fernandez-Lopez et al (2005) Jul-07
14 3780 1241 GAC GAG Asp Glu 2 ? C>G ? moderate, no other mutation found Jayandharan et al (2005) Aug-07
14 3864 1269 TCA TCC Ser Ser ? ? A/C 0.937/0.063; 0.82/0.18* - Higuchi et al (1991b); Lin et al (1993) Dec-91
14 3864 1269 TCA TCC Ser Ser ? ? A>C ? severe, also has K946X Klopp et al (2002) Dec-02
14 3864 1269 TCA TCC Ser Ser ? ? A>C ? severe, also has frameshift ins Klopp et al (2002) Dec-02
14 3864 1269 TCA TCC Ser Ser ? ? A>C ? severe, also has frameshift ins Klopp et al (2002) Dec-02
14 3864 1269 TCA TCC Ser Ser ? ? A>C ? severe, also has frameshift ins Klopp et al (2002) Dec-02
14 3931 1288 GTA GTC Val Val ? ? A/C 0.937/0.063 - Higuchi et al (1991b) Dec-91
14 4440 1462 CTG CCG Leu Pro ? ? T/C ? - Higuchi et al (1991a) Dec-91
14 4521 1488 ACA ACC Thr Thr ? ? A/C ? - Higuchi et al (1991a) Dec-91
17 4521 1882 ATC ATA Ile Ile 8 ? C/A ? mild, no other mutation found Jayandharan et al (2005) Aug-07
24 6642 2195 TAC TAT Tyr Tyr ? ? C/T ? - Antonarakis et al (unpub) Dec-91
25 6724 2223 GTG ATG Val Met ? ? ? ? PM on normal X of carrier Chan et al (1996) Dec-96
25 6724 2223 GTG ATG Val Met ? ? G/A 0.97/0.03; 0.02/0.98* (?error) - Antonarakis et al (unpub); Lin et al (1993) Dec-93
25 6724 2223 GTG ATG Val Met 101 ? G/A ? - Sommer et al (unpublished) Dec-90
25 6724 2223 GTG ATG Val Met ? ? G/A 0.98/0.02 - Gau et al (2006) Jun-07
25 6745 2230 CTG TTG Leu Leu 6 ? C/T ? also has Phe679Leu Timur et al (2001) Oct-01
25 6769 2238 ATG GTG Met Val <2 ? A/G 42% heterozygosity in Afro-Caribbean* previously thought to be causative Williams et al (1998) Jul-98
N/A 8728 110nt 5' poly A 3' untrans - ? ? A/G ?; 0.68/0.32 - Gitschier et al (1984); Higuchi et al (1991a) Dec-91
N/A 8728 110nt 5' poly A 3' untrans - ? ? A/G ? mild, no other mutation found Klopp et al (2002) Dec-02
N/A 8728 110nt 5' poly A 3' untrans - ? ? A/G ? severe, no other mutation found Klopp et al (2002) Dec-02
N/A 8728 110nt 5' poly A 3' untrans - ? ? A/G ? severe, also has Y813X Klopp et al (2002) Dec-02
N/A 8728 110nt 5' poly A 3' untrans - ? ? A/G ? severe, also has K946X Klopp et al (2002) Dec-02
N/A 8728 110nt 5' poly A 3' untrans - ? ? A/G ? severe, also has frameshift ins Klopp et al (2002) Dec-02
N/A 8728 110nt 5' poly A 3' untrans - ? ? A/G ? severe, also has frameshift ins Klopp et al (2002) Dec-02