Insertions in the factor VIII gene causing haemophilia A
08-May-12
Please note that codon/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 20 to negative numbers below and 19 to positive numbers:   
e.g. Met-19 becomes Met+1 but Arg+3 becomes Arg+22.            
Nucleotide numbering where given should conform to the convention that "A" in initiation codon ATG = +1  
Recommended syntax for sequence variations may be seen at   
http://www.genomic.unimelb.edu.au/mdi/mutnomen/          
Exon Nature of Insertion FVIII:C FVIII:Ag Severity Inhibitors Comments Reference Date added to HADB
1 1bp (T at codon 24) <1 ? Severe No frameshift Silva Pinto et al (unpublished) Aug-04
2 10bp (TTCCATTCAA at codon 38) <1 ? Severe ? frameshift Lin et al (1993) Dec-93
2 1bp (A in 5As at codons 47-48) <1 ? Severe ? frameshift Lillicrap et al (unpublished) Aug-05
2 2bp (GA at codon 48-9) nt 203-4 <1 ? Severe Yes frameshift Habart et al (2003) Aug-05
2 del G ins TT (GT>TTT at codon 103) nt 358-9 <1 ? ? No indel frameshift Habart et al (2003) Aug-05
4 9bp(GTCTTCCCT at codon 130) 2 ? Moderate No in frame deletion Ljung et al (unpublished) Jul-07
4 8bp (TCAAGATA at nt 514) <1 ? Severe No frameshift Timur et al (2001) Oct-01
5 1bp (T at codon 195) ? ? Severe ? frameshift Lillicrap et al (unpublished) Oct-02
6 2bp (GTA>GTCCA at codon 238) <1 ? Severe No frameshift Goodeve et al (2000) Feb-01
6 23bp (GGTTATGTAAACAGGTCTCTGCC at codon 243) <1 ? Severe No frameshift Liu et al (2002) Mar-02
7 1bp (A at codon 267) nt 858 ? ? ? No frameshift Habart et al (2003) Aug-05
8 1bp (T at codon 339) <1 ? Severe Yes frameshift Tagariello et al (unpublished) Apr-00
9 1bp (C at codons 426-427) <1 ? Severe No frameshift Lillicrap et al (unpublished) Aug-05
9 1bp (A at codon 429) <1 ? Severe No frameshift Gallardo et al (unpublished) Nov-06
9 1bp (C at codon 453) ? ? Severe ? frameshift Cutler et al (2002) Mar-02
9 1bp (A at nt 1441, codon 462) ? ? Severe ? frameshift Leuer et al (2001) Jul-07
9 2bp (TG at nt 1443, codon 462) ? ? Severe ? frameshift Leuer et al (2001) Jul-07
11 1bp (G at codon 513) ? ? Severe ? frameshift Economou et al (1992) Dec-92
12 3bp (ATC at codon 613) <1 ? Severe No in-frame Lavergne et al (unpublished) Dec-94
13 ins A del TG at codon 622 <1 ? Severe ? indel frameshift Gallardo et al (unpublished) Nov-06
13 1bp (A at codon 669) <1 ? Severe No frameshift Seehafer et al (unpublished) Dec-94
13 duplication of exon 13 by illegitimate recombination 10 ? Mild No in-frame   Casula et al, Murru et al (1990); Acquila et al, 2004A Dec-90
14 Alu repeat ? ? Severe ? large insertion Sukarova et al (2001) Mar-02
14 3.8 Kb LINE element ? ? Severe ? large insertion Kazazian et al (1988) Dec-88
14 2.1 Kb LINE element ? ? Severe Yes large insertion Kazazian et al (1988) Dec-88
14 1bp (A at codon 704-5) nt 2164 <1 ? ? No frameshift Habart et al (2003) Aug-05
14 5bp (AAATG at codon 706-7) nt 2176-2180 <1 ? ? No frameshift Habart et al (2003) Aug-05
14 c.2208_2214del / c.2207_2215insCTCTT Y718fs <1 ? Severe Yes indel frameshift Bogdanova et al (2002, 2005) Dec-02
14 1bp (G at codon 772) <1 <1 Severe No frameshift Ivaskevicius et al (2001) Aug-01
14 13bp duplication at codons 836-840 <1 ? Severe No frameshift Fidalgo et al (unpublished) Aug-04
14 1bp (T at codon 833), del GA 1 ? Severe No frameshift Lillicrap et al (unpublished) Dec-97
14 1bp (T at codon 847) <1 ? Severe No frameshift Gallardo et al (unpublished) Nov-06
14 del GGGACAACT/ins CTGCAGTT at 864-6 <1 <1 Severe Yes indel Nakaya et al (2001) Mar-02
14 delGACA insCAATTAAATGAGAA <1 ? Severe No indel Jayandharan et al (2005) Aug-07
14 13bp duplication at codons 883-887 ? ? Severe ? frameshift Laprise et al (1998) Jan-99
14 1bp (T at nt2739, codon 894) <1 <1 Severe No frameshift Ljung et al (unpublished); Leuer et al (2001) Oct-99
14 insA Lys>fs (TGA-984) <1 ? Severe No frameshift Jayandharan et al (2005) Aug-07
14 N963fs  c.2945dupA <1 ? Severe No frameshift Naylor et al (1993b) Dec-93
14 N963fs  c.2945dupA <1 ? Severe No frameshift Nakaya et al (2001) Mar-02
14 N963fs  c.2945dupA <1 ? Severe No frameshift Bogdanova et al (2002, 2005) Dec-02
14 N963fs  c.2945dupA <1 ? Severe No frameshift Silva Pinto et al (unpublished) Aug-04
14 N963fs  c.2945dupA <1 ? ? No frameshift Habart et al (2003) Aug-05
14 N963fs  c.2945dupA 1 ? Severe No frameshift Lillicrap et al (unpublished) Aug-05
14 N963fs  c.2945dupA <1 ? Severe No frameshift Bogdanova et al (2005) Jul-06
14 N963fs  c.2945dupA 1 ? Severe No frameshift Arnold et al (unpublished) Jul-06
14 2bp (TC at codon 1031-2) <1 <1 Severe Yes frameshift Nakaya et al (2001) Mar-02
14 N1073fs  c.3275dupA <1 ? Severe No frameshift Hill et al (2005) Nov-05
14 N1073fs  c.3275dupA <1 ? Severe No frameshift Bogdanova et al (2005) Jul-06
14 1bp (A in 6As at codon 1080-1) ? ? Severe No frameshift Pieneman et al (1995) Jun-96
14 1bp (A in 6As at codon 1080-1) 1 ? Moderate Yes frameshift Nakaya et al (2001) Mar-02
14 1bp (A in 6As at codon 1080-1) ? ? Severe No frameshift Klopp et al (2002) Dec-02
14 16bp dupl (GGGCCCCATTCCACCA) at codon 1082-1087 <1 ? Severe ? frameshift Ahmed et al (2005) Aug-05
14 8bp (AAAGAGGG at codon 1083) <1 ? Severe No frameshift Fernandez-Lopez et al (2005) Jul-07
14 1bp (T at codon 1100) <1 ? Severe Yes frameshift Cutler et al (2002) May-02
14 1bp (T at codon 1120) ? ? Severe ? frameshift Klopp et al (2002) Dec-02
14 1bp (AA>AAA at codon 1169-70) <1 <1 Severe Yes frameshift Nakaya et al (2001) Mar-02
14 5bp (AAACC at codons 1172 or 1174) ? ? ? No frameshift Lillicrap et al (unpublished) Oct-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA ? ? Severe ? frameshift Pieneman et al (1995) Jun-96
14 1bp (A in 9As at codon 1191-4) 3637_3638insA ? ? Severe ? frameshift Becker et al (1996) Aug-96
14 1bp (A in 9As at codon 1191-4) 3637_3638insA <1 ? Severe No frameshift Freson et al (1998) Apr-99
14 1bp (A in 9As at codon 1191-4) 3637_3638insA 1,2,3 25 (post) Moderate No frameshift Nakaya et al (2001) Mar-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA 1,5 1 Moderate No frameshift Nakaya et al (2001) Mar-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA 1-2 <1 Moderate No frameshift Nakaya et al (2001) Mar-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA <1-1 <1 Severe No frameshift Nakaya et al (2001) Mar-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA 1 ? Severe No frameshift Lillicrap et al (unpublished) Oct-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA <1 ? Severe No frameshift Lillicrap et al (unpublished) Oct-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA <1 ? Severe No frameshift Lillicrap et al (unpublished) Oct-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA 1 ? Severe No frameshift Lillicrap et al (unpublished) Oct-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA <1 ? Severe ? frameshift Lillicrap et al (unpublished) Aug-05
14 1bp (A in 9As at codon 1191-4) 3637_3638insA ? ? Severe No frameshift Klopp et al (2002) Dec-02
14 1bp (A in 9As at codon 1191-4) 3637_3638insA 3 4 Severe ? frameshift Cai et al (2006) Jun-07
14 1bp (A in 9As at codon 1191-4) 3637_3638insA <1 <1 Severe No frameshift Ljung et al (unpublished) Jul-07
14 1bp (A in 9As at codon 1191-4) 3637_3638insA Ile>fs TAA-1220 <1 ? Severe No frameshift Jayandharan et al (2005) Aug-07
14 1bp (A in 7As at codons 1269-71) 9 ? Mild No misread rescue? Frusconi et al (2002) Nov-02
14 1bp (A in 7As at codons 1269-71) <1 ? Severe Yes frameshift Hill et al (2005) Nov-05
14 2bp (AA at codon 1324) <1 ? Severe ? frameshift Lin et al (1993) Dec-93
14 4 and 1bp (ATCT at codon 1372, T at 1373) <1 ? Severe No frameshift Williams et al (1998) Jul-98
14 1bp (TCA to TCAA at codon 1395) <1 ? Severe ? frameshift Higuchi et al (1991b) Dec-91
14 c.4329_4330insA  p.D1425fsX18 <1 ? Severe No frameshift Riccardi et al (unpublished) Nov-05
14 1bp (G in 4Gs at codon 1427-8) <1 ? Severe No frameshift Vidal et al (2001) Aug-01
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe ? frameshift Higuchi et al (1991b) Dec-91
14 c.4379_4380insA p.N1441KfsX2 1.4 1.0 Severe No frameshift David et al (1994) Dec-95
14 c.4379_4380insA p.N1441KfsX2 ? ? Severe No frameshift Pieneman et al (1995) Jun-96
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Freson et al (1998) Apr-99
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Goodeve et al (2000) Feb-01
14 c.4379_4380insA p.N1441KfsX2 3 ? Moderate No frameshift Akkarapatumwong et al (2000) Feb-01
14 c.4379_4380insA p.N1441KfsX2 <1 <1 Severe ? frameshift Ljung et al (unpublished) Oct-99
14 c.4379_4380insA p.N1441KfsX2 <1 <1 Severe No frameshift Ivaskevicius et al (2001) Aug-01
14 c.4379_4380insA p.N1441KfsX2 <1 <1 Severe No frameshift Ivaskevicius et al (2001) Aug-01
14 c.4379_4380insA p.N1441KfsX2 <1 <1 Severe No frameshift Nakaya et al (2001) Mar-02
14 c.4379_4380insA p.N1441KfsX2 1,2,4 <1 Moderate No frameshift Nakaya et al (2001) Mar-02
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Nakaya et al (2001) Mar-02
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Nakaya et al (2001) Mar-02
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Cutler et al (2002) Aug-02
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Lillicrap et al (unpublished) Oct-02
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Lillicrap et al (unpublished) Oct-02
14 c.4379_4380insA p.N1441KfsX2 1 ? Severe No frameshift Lillicrap et al (unpublished) Oct-02
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Lillicrap et al (unpublished) Oct-02
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Lillicrap et al (unpublished) Aug-05
14 c.4379_4380insA p.N1441KfsX2 ? ? Severe No frameshift Klopp et al (2002) Dec-02
14 c.4379_4380insA p.N1441KfsX2 <1 ? ? ? frameshift Citron et al (2002) Aug-03
14 c.4379_4380insA p.N1441KfsX2 <1 ? ? No frameshift Habart et al (2003) Aug-05
14 c.4379_4380insA p.N1441KfsX2 <1 ? ? No frameshift Habart et al (2003) Aug-05
14 c.4379_4380insA p.N1441KfsX2 ? ? Severe ? frameshift Western et al (unpublished) Aug-05
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Riccardi et al (unpublished) Nov-05
14 c.4379_4380insA p.N1441KfsX2 1 ? Severe No frameshift Arnold et al (unpublished) Jul-06
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe ? frameshift Gallardo et al (unpublished) Nov-06
14 c.4379_4380insA p.N1441KfsX2 <1 ? Severe No frameshift Acquila et al (2004B) Jul-07
14 c.4379_4380insA p.N1441KfsX2 <1 <1 Severe No frameshift Ljung et al (unpublished) Jul-07
14 insA 1441 <1 ? Severe No frameshift Jayandharan et al (2005) Aug-07
14 insA 1441 <1 ? Severe No frameshift Jayandharan et al (2005) Aug-07
14 31bp (after codon 1485) <1 ? Severe No frameshift Cutler et al (2002) Aug-02
14 1bp (A at codon 1495; nt4542) <1 ? ? ? frameshift Citron et al (2002) Aug-03
14 1bp (A at codon 1495; nt4542) <1 ? ? ? frameshift Citron et al (2002) Aug-03
14 c.4665_4688del / 4664_4689insAAGGAA N1536fs <1 ? Severe Yes indel frameshift Bogdanova et al (2002, 2005) Dec-02
14 del AT ins G (AAAAT>AAAG at codon 1543) nt 4683 <1 ? ? No indel frameshift Habart et al (2003) Aug-05
14 T1590fs  c.4825dupA <1 ? Severe ? frameshift Lin et al (1993) Dec-93
14 T1590fs  c.4825dupA <1 ? Severe No frameshift Freson et al (1998) Apr-99
14 T1590fs  c.4825dupA <1 ? Severe No frameshift Goodeve et al (2000) Feb-01
14 T1590fs  c.4825dupA <1 ? Severe No frameshift Nakaya et al (2001) Mar-02
14 T1590fs  c.4825dupA <1 <1 Severe No frameshift Nakaya et al (2001) Mar-02
14 T1590fs  c.4825dupA 0.8 ? Severe No frameshift Lillicrap et al (unpublished) Oct-02
14 T1590fs  c.4825dupA <1 ? Severe No frameshift Bogdanova et al (2002, 2005) Dec-02
14 T1590fs  c.4825dupA ? ? Severe Yes frameshift Klopp et al (2002) Dec-02
14 T1590fs  c.4825dupA <1 ? Severe No frameshift Gallardo et al (unpublished) Aug-03
14 T1590fs  c.4825dupA 1 ? ? No frameshift Habart et al (2003) Aug-05
14 T1590fs  c.4825dupA <1 ? Severe ? frameshift Ahmed et al (2005) Aug-05
14 1bp (T) at codon 1613: stop at 1615 <1 ? Severe No frameshift Acquila et al (2004B) Jul-07
14 1bp (A at codon 1645; nt4991) <1 ? ? ? frameshift Citron et al (2002) Aug-03
14 1bp (A at codon 1645; nt4991) <1 ? ? ? frameshift Citron et al (2002) Aug-03
14 ins 2bp (TG in codon 1667-71), del ATATCAGTTGAA <1 ? Severe No indel frameshift Lillicrap et al (unpublished) Oct-02
14 2bp(TC at codon 1686) 1 7 Sev/Mod No frameshift Ljung et al (unpublished) Jul-07
14 41bp Frameshift <1 ? Severe No frameshift Gallardo et al (unpublished) Aug-00
17 1bp (T at codon 1855) <1 ? Severe No frameshift Becker et al (1996) Aug-96
17 4bp (TGAA at codons 1863-1864) 1 ? Severe No frameshift Lillicrap et al (unpublished) Aug-05
17 1bp (T at codon 1880) ? ? Severe ? frameshift Klopp et al (2002) Dec-02
17 1bp (A in 4As at codon 1888) ? ? Severe ? frameshift Higuchi et al (1991b) Dec-91
17 del TG & ins 20 (TCATCAAAGTACTTCAAAAA in codon 1888) 3 ? Moderate No in-frame indel Liu et al (2002) Mar-02
18 2bp (TA in codon 1934) <1 ? Severe ? frameshift Yenchitsomanus et al (2003) Aug-04
18 1bp (A in codon 1956) <1 <1 Severe No frameshift Pieneman et al (1995) Jun-96
18 1bp (A in 7As in codon 1966-9) <1 <1 Severe No frameshift Pieneman et al (1995) Jun-96
18 1bp (A in 7As in codon 1966-9) <1 <1 Severe Yes frameshift Liu et al (1998) Mar-99
18 4bp (GGAG in codon 1971) ? ? Severe Yes frameshift Klopp et al (2002) Dec-02
19 1bp (C in codon 2005) 2 ? Moderate ? frameshift Ahmed et al (2005) Aug-05
19 1bp (G in codon 2011) <1 ? Severe No frameshift Gallardo et al (unpublished) Aug-03
19 del C / ins TT at codon 2013 (c.6094) <1 ? Severe ? indel frameshift Ahmed et al (2005) Aug-05
19 Alu Yb9 element insertion into intron 19 <1 ? Severe ? exon 19 skip Ganguly et al (2003) Jun-07
20 1bp (ATG>AATG codon 2027) 2 ? Severe ? frameshift Nesbitt et al (unpublished) Feb-01
20 c.6165_6166dupGA p.I2037RfsX40 <1 ? Severe No frameshift Riccardi et al (unpublished) Oct-06
21 S2069fs  c.6202_6257dup <1 ? Severe No frameshift Bogdanova et al (2002, 2005) Dec-02
22 2bp (AC in codon 2088) <1 <1 Severe No frameshift Pieneman et al (1995) Jun-96
22 2bp (CA in codon 2098) <1 ? Severe Yes frameshift Gallardo et al (unpublished) Aug-03
22 1bp(A at codon 2101) <1 <1 Severe No frameshift Ljung et al (unpublished) Jul-07
24 1bp (A in codon 2184-5) <1 0 Severe No frameshift Liu et al (2000) Apr-00
24 1bp (A in codon 2199) <1 ? ? ? frameshift Chan et al (1996) Dec-96
25 CAA inframe insertion of Gln after Val 2243  2 ? Moderate ? in-frame   Bicocchi et al (2003) Aug-04
25 4bp (ACTA) in codon 2245 <1 ? Severe Yes frameshift Akkarapatumwong et al (1999) Nov-99
25 insertion/deletion <1 ? ? ? indel Citron et al (2002) Jul-03