| Listing
of all reported Splice Mutations in the FVIII Gene |
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| 08-May-12 |
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| Please
note that aminoacid numbering given below is for the mature processed
protein, as used almost universally in FVIII studies. |
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| To
convert to HGVS-type aminoacid numbering (where initiator Met =+1) add 19 to
aminoacid numbers. |
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| Nucleotide
numbering where given should conform to the convention that "A" in
initiation codon ATG = +1 |
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| Recommended
syntax for sequence variations may be seen at |
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| http://www.genomic.unimelb.edu.au/mdi/mutnomen/ |
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| Exon/Intron |
Aminoacid |
Nucleotide Change |
Aminoacid Change |
FVIII:C (%) |
FVIII:Ag (%) |
Severity |
Inhibitors |
Comments |
References |
Date added to HADB |
| 1 |
Intron |
a>g |
- - |
? |
? |
Severe |
? |
New donor splice ~1.3KB 3' of exon1 |
Western et al (unpublished) |
Aug-05 |
| 1 |
Intron |
a>g |
- - |
2 |
? |
Moderate |
No |
New donor splice 1.4KB 3' of exon1 |
Bagnall et al (1999) |
Feb-00 |
| 1 |
Intron |
a>g |
- - |
<1 |
? |
Moderate |
No |
New donor splice 1.4KB 3' of exon1 |
Bagnall et al (1999) |
Feb-00 |
| 1 |
Intron |
IVS1+2T>C |
- - |
21 |
18 |
Mild |
No |
IVS1+2T>C |
Casana et al (2004) |
Jul-07 |
| 1 |
29 |
AGA>AAA |
Arg Lys |
<1 |
? |
Severe |
No |
-1 IVS1 acceptor splice site |
Becker et al (1996) |
Aug-96 |
| 1 |
In1/Ex2 |
GA>AA |
? ? |
2 |
? |
Severe |
No |
-1 IVS1 acceptor splice site |
Timur et al (2001) |
Oct-01 |
| 1 |
In1/Ex2 |
a>g |
? ? |
<1 |
? |
Severe |
No |
-2bp ex2 acceptor splice |
Liu et al (2002) |
Mar-02 |
| 1 |
Intron |
(-26) A>T c.-143 |
- - |
<1 |
? |
Severe |
No |
(-26) A>T c.-143 |
Jayandharan et al (2005) |
Aug-07 |
| 2 |
Intron |
tcttcacgcag/A>gcttcacgcag/A |
- - |
3-5 |
? |
? |
No |
- |
Lillicrap et al (unpublished) |
Oct-02 |
| 2 |
Intron |
G/g>G/a |
- - |
2 |
45 |
Severe |
No |
Donor splice intron 2 |
Liu et al (1998) |
May-99 |
| 2 |
Intron |
cga>tga |
- - |
<1 |
? |
Severe |
No |
300bp 3' to exon 2 |
Gitschier et al (1985) |
Dec-85 |
| 2 |
Intron |
cag>caa |
- - |
2 |
? |
Severe |
No |
Acceptor splice |
Timur et al (2001) |
Oct-01 |
| 2 |
Intron |
G265+1A |
- - |
<1 |
? |
Severe |
No |
Splice donor |
Goodeve et al (2000) |
Feb-01 |
| 3 |
Intron |
c.294-2A>T |
- - |
1 |
? |
Severe |
? |
-3 IVS3 |
Ahmed et al (2005) |
Aug-05 |
| 3 |
Intron |
c>t |
- - |
31 |
? |
Mild |
No |
-9 IVS3 also Val1857Leu |
Timur et al (2001) |
Oct-01 |
| 3 |
70 |
GGT>GAT |
Gly Asp |
<1 |
? |
Severe |
No |
-1 IVS2 donor splice site |
Becker et al (1996) |
Aug-96 |
| 3 |
Intron |
g>a |
- - |
? |
? |
Severe |
No |
5nt past end exon 3 |
Klopp et al (2002) |
Dec-02 |
| 3 |
Intron |
AGG/gtgag>AGG/gtgaa |
- - |
<1 |
? |
Severe |
No |
IVS3+5 donor splice site |
Fidalgo et al (unpublished) |
Aug-04 |
| 3 |
Intron |
IVS3+5G>A |
- - |
<1 |
? |
Severe |
No |
IVS3+5 donor splice site |
Riccardi et al (unpublished) |
Nov-05 |
| 3 |
Intron |
AG/>TG/ |
- - |
<1 |
? |
Severe |
Yes |
-2 IVS3 acceptor splice
site |
Riccardi et al (unpublished) |
Jan-04 |
| 4 |
Intron |
c.601+5G>A |
- - |
9 |
? |
Mild |
? |
+5 IVS4 |
Ahmed et al (2005) |
Aug-05 |
| 4 |
Intron |
cga>caa |
- - |
5-10 |
41 |
Mild |
No |
May activate cryptic splice |
Youssouffian et al (1988c) |
Dec-88 |
| 4 |
Intron |
tctttttcag/GG>gctttttcag/GG |
- - |
7 |
? |
Mild |
No |
splicing error |
Gallardo et al (unpublished) |
Nov-06 |
| 4 |
Intron |
ag/GG>aa/GG |
- - |
<1 |
? |
Severe |
No |
-1 IVS4 acceptor splice
site |
Fernandez-Lopez et al (2005) |
Jul-07 |
| 4 |
Intron |
ag/>gg/ |
- - |
2 |
1 |
Severe |
No |
-2 IVS4 acceptor splice site |
David et al (1994) |
Dec-94 |
| 5 |
Intron |
nt6 T>C |
- - |
3 |
? |
? |
? |
IVS 5 Ggttagtga>Ggttagcga |
Chan et al (1996) |
Dec-96 |
| 5 |
Intron |
nt6 T>C |
- - |
10 |
? |
? |
? |
IVS 5 Ggttagtga>Ggttagcga |
Chan et al (1996) |
Dec-96 |
| 5 |
Intron |
G>A |
- - |
<1 |
? |
? |
? |
IVS5 +5G>A |
Citron et al (2002) |
Jul-03 |
| 5 |
205 |
G/GG>T/GG |
Gly Trp |
3 |
? |
Moderate |
? |
-1 IVS5 donor splice site |
Higuchi et al (1991a) |
Dec-91 |
| 5 |
Intron |
C>G |
- - |
<1 |
? |
Severe |
? |
-3 IVS5 acceptor, deletes Ex6/5&6 |
Tavassoli et al (1998) |
Jan-99 |
| 5 |
Intron |
del 12 nt actctatctttg |
- - |
12 |
? |
Mild |
No |
small deletion splicing error |
Gallardo et al (unpublished) |
Nov-06 |
| 5 |
Intron |
ag/>gg/ |
- - |
<1 |
? |
Severe |
No |
-2 IVS5 acceptor splice site |
Naylor et al (1991) |
Dec-91 |
| 5 |
Intron |
A>G |
- - |
<1 |
? |
Severe |
No |
IVS 5 670-2: also M2238V polymorphism |
Williams et al (1998) |
Jul-98 |
| 5 |
Intron |
A>G |
- - |
<1 |
? |
Severe |
No |
IVS5 c.671-2 A>G: |
Williams et al (1998) |
Jul-98 |
| 5 |
Intron |
G/gt>G/gg |
- - |
? |
? |
Severe |
No |
- |
Lillicrap et al (unpublished) |
Oct-02 |
| 5 |
Intron |
IVS5+1G>T |
- - |
<1 |
? |
Severe |
No |
IVS5+1G>T |
Riccardi et al (unpublished) |
Nov-05 |
| 5 |
Intron |
IVS5 613+5G>A |
- - |
4 |
? |
Severe |
No |
IVS5 +5G>A |
Arnold et al (unpublished) |
Jul-06 |
| 6 |
Intron |
ctttacag/GT>gtttacag/GT |
- - |
? |
? |
Mild |
? |
splicing error |
Gallardo et al (unpublished) |
Nov-06 |
| 6 |
Intron |
ag/>ac/ |
- - |
? |
? |
Severe |
? |
-1 IVS6 acceptor splice site |
Antonarakis et al (unpublished) |
Dec-91 |
| 6 |
Intron |
ag/>at/ |
- - |
<1 |
? |
Severe |
? |
-1 IVS6 acceptor splice site |
Bicocchi et al (2003) |
Aug-04 |
| 6 |
Exon |
CCA>CCC |
Pro Pro |
25 |
75 |
Mild |
No |
-2 IVS6 donor splice site ?causative |
Liu et al (1998) |
May-99 |
| 6 |
Intron |
G/gta>G/gtg |
- - |
5 |
? |
Moderate |
? |
+3 IVS6 donor splice site |
Nesbitt et al (unpublished) |
Aug-05 |
| 6 |
Intron |
G/gta>G/gtg |
- - |
3 |
? |
Moderate |
No |
+3 IVS6 donor splice site |
Bidichandani et al (1994) |
Dec-94 |
| 6 |
Intron |
G/gta>G/gtg |
- - |
3-4 |
? |
Moderate |
No |
+3 IVS6 donor splice site |
Bidichandani et al (1994) |
Dec-94 |
| 6 |
Intron |
G/gta>G/gtg |
- - |
<1 |
? |
Severe |
No |
+3 IVS6 donor splice site |
Theophilus et al (2001) |
Aug-01 |
| 6 |
Intron |
G/gta>G/gtg |
- - |
<1 |
<1 |
Severe |
No |
+3 IVS6 donor splice site |
Ljung et al (unpublished) |
Jul-07 |
| 6 |
Intron |
AG/gta>AG/ata |
- - |
<1 |
? |
Severe |
No |
+1 IVS6 donor splice site |
Gallardo et al (unpublished) |
Nov-06 |
| 7 |
Intron |
c.1009+3A>C |
- - |
2 |
? |
Mild |
? |
IVS7 +3 |
Ahmed et al (2005) |
Aug-05 |
| 7 |
Intron |
c.1009+1G>A |
- - |
<1 |
? |
Severe |
? |
IVS7 +1 |
Ahmed et al (2005) |
Aug-05 |
| 7 |
Intron |
ag/ATG>cg/ATG |
- - |
<1 |
? |
Severe |
No |
IVS7-2 acceptor splice site |
Silva Pinto et al (unpublished) |
Aug-04 |
| 7 |
Intron |
TG/gta>TG/ata |
- - |
<1 |
? |
Severe |
No |
+1 IVS7 donor splice site |
Gallardo et al (unpublished) |
Nov-06 |
| 7 |
Intron |
(-23) G>A |
- - |
<1 |
? |
Severe |
No |
polymorphism? |
Jayandharan et al (2005) |
Aug-07 |
| 8 |
Intron |
G>A |
- - |
<1 |
? |
Severe |
? |
+1 IVS8 donor splice site |
Cutler et al (2002) |
May-02 |
| 9 |
Intron |
nt1 G>A |
- - |
3 |
? |
? |
? |
IVS 9 Ggtaagtt>Gataagtt |
Chan et al (1996)) |
Dec-96 |
| 9 |
Exon |
1443G>A codon 462 |
Leu Leu |
12 |
? |
Mild |
? |
1443G>A at end exon 9 |
Ahmed et al (2005) |
Aug-05 |
| 9 |
Intron |
c.1443+5G>C |
- - |
1 |
? |
Moderate |
? |
IVS 9 +5 |
Ahmed et al (2005) |
Aug-05 |
| 9 |
Intron |
c.1443+18T>G |
- - |
1 |
? |
Moderate |
? |
IVS 9 +18 |
Ahmed et al (2005) |
Aug-05 |
| 9 |
Exon |
1443G>A codon 462 |
Leu Leu |
8 |
? |
Mild |
No |
1443G>A at end exon 9 |
Casey et al (unpublished) |
Aug-04 |
| 9 |
Intron |
#2 T>C |
- - |
<1 |
? |
Severe |
Yes |
IVS 9 #2 T>C |
Casey et al (unpublished) |
Aug-04 |
| 10 |
Intron |
AG/gtaaatattc>AG/gtaaatattg |
- - |
NA carrier |
? |
NA carrier |
? |
splice error in carrier only |
Gallardo et al (unpublished) |
Nov-06 |
| 10 |
Intron |
c.1473-2A>G |
- - |
<1 |
? |
Severe |
? |
IVS 10 -2 |
Ahmed et al (2005) |
Aug-05 |
| 10 |
Intron |
ag/GT>at/GT |
- - |
<1 |
? |
? |
No |
acceptor site lost |
Habart et al (2003) |
Aug-05 |
| 10 |
Intron |
(-2) A>G c.1538 |
- - |
<1 |
? |
Severe |
No |
also has IVS9 (+18) T>G (poly?) |
Jayandharan et al (2005) |
Aug-07 |
| 11 |
Intron |
nt5 G>A |
- - |
7 |
? |
? |
? |
IVS 11 Ggtgagtt>Ggtgaatt |
Chan et al (1996) |
Dec-96 |
| 11 |
504 |
CTG>CTT |
Leu Leu |
? |
? |
Mild |
? |
Potential new acceptor site |
Diamond et al (1992) |
Dec-92 |
| 11 |
504 |
CTG>CTT |
Leu Leu |
8-14 |
? |
Mild |
? |
Cryptic splice del 36bp Exon 11 |
Tavassoli et al (1998) |
Jan-99 |
| 11 |
504 |
CTG>CTT |
Leu Leu |
? |
? |
Mild |
No |
Potential new acceptor site |
Economou et al (1992) |
Dec-92 |
| 11 |
504 |
CTG>CTT |
Leu Leu |
? |
? |
Mild |
No |
Potential new acceptor site |
Economou et al (1992) |
Dec-92 |
| 11 |
504 |
CTG>CTT |
Leu Leu |
? |
? |
Mild |
No |
Potential new acceptor site |
Economou et al (1992) |
Dec-92 |
| 11 |
504 |
CTG>CTT |
Leu Leu |
7 |
? |
Mild |
No |
Potential new acceptor site |
Vidal et al (2001) |
Aug-01 |
| 11 |
565 |
CAG>AAG |
Gln Lys |
? |
? |
Mild/Moderate |
No |
/gt -3 IVS11 donor splice site |
Higuchi et al (1991a) |
Dec-91 |
| 11 |
565 |
CAG>AAG |
Gln Lys |
? |
? |
Moderate |
No |
/gt -3 IVS11 donor splice site |
Antonarakis et al (unpublished) |
Dec-91 |
| 11 |
Intron |
G>A |
- - |
<1 |
? |
Severe |
No |
IVS 11 c.1753-1 G>A |
Bogdanova et al (2005) |
Jul-06 |
| 12 |
Intron |
/gtgagt>/gtgaat |
- - |
? |
? |
Mild |
? |
+5 IVS12 donor splice site |
Antonarakis et al (unpublished) |
Dec-91 |
| 12 |
Intron |
A/gt>A/at |
- - |
? |
? |
Severe |
? |
- |
Lillicrap et al (unpublished) |
Oct-02 |
| 12 |
Intron |
del G |
- - |
? |
? |
Severe |
? |
1903 +3 del G donor splice |
Nesbitt et al (unpublished) |
Aug-05 |
| 12 |
Intron |
agt>att |
- - |
6 |
117 |
Mild |
No |
Ex12 +5 donor splice site ?causative |
Liu et al (1998) |
May-99 |
| 13 |
616 |
A/GC > A/AC |
Ser Asn |
6-28 |
30 |
Mild |
No |
acceptor splice |
Liu et al (2002) |
Mar-02 |
| 13 |
Intron |
G/g>G/a |
- - |
<1 |
<1 |
Severe |
No |
-1IVS13 donor splice |
Ljung et al (unpublished) |
Jul-07 |
| 13 |
Intron |
cag>caa |
- - |
<1 |
7 |
Severe |
Yes |
Ex14 -1 acceptor splice site |
Liu et al (1998) |
May-99 |
| 14 |
Intron |
InsA |
- - |
<1 |
? |
? |
? |
IVS14 -16 InsA |
Citron et al (2002) |
Jul-03 |
| 14 |
Exon |
C5217T |
Asn 1720 |
39 |
? |
Mild |
? |
Splice |
Western et al (unpublished) |
Aug-05 |
| 14 |
Intron |
AG/gta>AG/gtg |
- - |
9 |
? |
Mild |
? |
Splice |
Nesbitt et al (unpublished) |
Aug-05 |
| 14 |
Intron |
ag/GTA>ag/GTG |
? ? |
<1 |
<3 |
Severe |
No |
-3 IVS14 acceptor splice site |
Seehafer et al (unpublished) |
Dec-96 |
| 14 |
Intron |
G>A |
- - |
<1 |
? |
Severe |
No |
IVS14-1 G>A |
Frusconi et al (2002) |
Nov-02 |
| 14 |
Intron |
G/gt>G/gg |
- - |
<1 |
? |
Severe |
No |
- |
Lillicrap et al (unpublished) |
Aug-05 |
| 14 |
Intron |
IVS14+3A>G |
- - |
? |
? |
Mild |
? |
IVS14+3A>G |
Lombardi et al (2004) |
Jul-07 |
| 15 |
Intron |
G>C |
- - |
<1 |
? |
? |
? |
IVS15 +1G>C |
Citron et al (2002) |
Jul-03 |
| 15 |
Intron |
G>A |
- - |
<1 |
? |
? |
? |
IVS15 +1G>A |
Citron et al (2002) |
Jul-03 |
| 15 |
Intron |
gtg>ttg |
- - |
<1 |
<1 |
Severe |
No |
Ex15 +1 donor splice site |
Liu et al (1998) |
May-99 |
| 15 |
Intron |
gtg>ttg |
- - |
<1 |
? |
Severe |
No |
Ex15 +1 donor splice site |
Yenchitsomanus et al (2001) |
Aug-01 |
| 15 |
Intron |
cag>ctg |
- - |
<1 |
? |
Severe |
No |
IVS15 acceptor site |
Tagariello et al (unpublished) |
Apr-00 |
| 15 |
Intron |
(+6) T>G c.5373 |
- - |
<1 |
? |
Severe |
No |
(+6) T>G c.5373 |
Jayandharan et al (2005) |
Aug-07 |
| 16 |
1843 |
CTG>CTA |
Leu Leu |
9-18 |
? |
Moderate |
? |
-1 IVS16 donor splice site |
Higuchi et al (1991a) |
Dec-91 |
| 16 |
Intron |
tag>taa |
- - |
<1 |
? |
Severe |
No |
-1 IVS16 acceptor splice site |
Vidal et al (2001) |
Aug-01 |
| 17 |
Intron |
gca/ATC>tca/ATC |
- - |
? |
? |
Severe |
? |
Int17/Ex18 Splice |
Nesbitt et al (unpublished) |
Aug-05 |
| 17 |
Intron |
t>c |
- - |
<1 |
? |
Severe |
No |
+2 IVS17 donor splice |
Liu et al (2002) |
Mar-02 |
| 18 |
Intron |
AG/g>AG/a |
- - |
<1 |
? |
Severe |
No |
Skip Exon 18/part Exon 19 |
Freson et al (1998) |
Apr-99 |
| 18 |
Intron |
AG/g>AG/a |
- - |
<1 |
? |
Severe |
No |
Skip Exon 18/part Exon 19 |
Theophilus et al (2001) |
Aug-01 |
| 18 |
Intron |
AG/g>AG/a |
- - |
2 |
? |
Severe |
No |
Skip Exon 18/part Exon 19 |
Lillicrap et al (unpublished) |
Oct-02 |
| 18 |
Intron |
(+91) G>A |
- - |
<1 |
? |
Severe |
No |
polymorphism? |
Jayandharan et al (2005) |
Aug-07 |
| 19 |
??? |
Agtg>Agtt |
?? |
? |
? |
Severe |
? |
Exon 19 donor splice site |
Lambert et al (1997) |
Apr-97 |
| 19 |
Intron |
A>G |
- - |
<1 |
? |
Severe |
? |
IVS19 -2 Del exon 20 |
Tavassoli et al (1998) |
Jan-99 |
| 19 |
Intron |
A/gt>A/gc |
- - |
<1 |
? |
Severe |
? |
- |
Lillicrap et al (unpublished) |
Aug-05 |
| 19 |
Intron |
Alu element insertion |
- - |
<1 |
? |
Severe |
? |
exon 19 skipped |
Ganguly et al (2003) |
Jun-07 |
| 19 |
Intron |
TA/gtgagtagc>TA/gtgagtagg |
- - |
23 |
? |
Mild |
No |
splicing error |
Gallardo et al (unpublished) |
Nov-06 |
| 19 |
Intron |
gtgagt>gtgaat |
- - |
1 |
? |
Severe |
No |
Excises exon 19 |
Tavassoli et al (1997) |
Aug-97 |
| 19 |
Intron |
ATA/gtgagt>ATA/gtgaga |
- - |
<1 |
? |
Severe |
No |
- |
Gallardo et al (unpublished) |
Sep-03 |
| 19 |
Intron |
G>A |
- - |
<1 |
0.3 |
Severe |
No |
IVS19 +1 G>A |
Ivaskevicius et al (2001) |
Aug-01 |
| 19 |
Intron |
A IVS19 +4G |
inserts Glu |
? |
? |
Severe |
No |
deletes exon 19 |
Bicocchi et al (2004); Bicocchi et al (2005B) |
Jul-07 |
| 21 |
Intron |
c.6273+1G>T |
- - |
<1 |
? |
Severe |
? |
IVS 21 +1 |
Ahmed et al (2005) |
Aug-05 |
| 22 |
Intron |
C>G |
- - |
<1 |
? |
? |
? |
IVS22 -3 |
Citron et al (2002) |
Jul-03 |
| 22 |
Intron |
g>t |
- - |
? |
? |
Moderate |
? |
5nt past end exon 22 |
Klopp et al (2002) |
Dec-02 |
| 22 |
Intron |
TG/g>TG/a |
- - |
<1 |
? |
Severe |
No |
- |
Lillicrap et al (unpublished) |
Oct-02 |
| 22 |
Intron |
t>a |
- - |
? |
? |
Severe |
No |
2nt past end exon 22 |
Klopp et al (2002) |
Dec-02 |
| 22 |
Intron |
g>t |
- - |
? |
? |
Severe |
No |
5nt past end exon 22 |
Klopp et al (2002) |
Dec-02 |
| 23 |
Intron |
G>A |
- - |
<1 |
? |
? |
? |
IVS23 -1 splice mutation |
Citron et al (2002) |
Jul-03 |
| 23 |
Intron |
A>C |
- - |
<1 |
? |
Severe |
? |
IVS23 +3 Donor splice mutation |
Moller-Morlang et al (1999) |
Oct-99 |
| 23 |
Intron |
Agta>Aata |
- - |
<1 |
? |
Severe |
No |
Donor splice mutation |
Strmecki et al (1999) |
Oct-99 |
| 23 |
Intron |
agt>act |
- - |
<1 |
? |
Severe |
No |
IVS23 +5 Donor splice mutation |
Vidal et al (2001) |
Aug-01 |
| 24 |
2213 |
CAA>CAG |
Gln Gln |
? |
? |
? |
? |
Possible cryptic splice site |
McVey et al (unpublished) |
Dec-96 |
| 24 |
Intron |
T>A |
- - |
7 |
? |
Mild |
? |
-4 IVS24 acceptor splice site |
Cutler et al (2002) |
May-02 |
| 24 |
2173 |
A/GT > A/TT |
Ser Ile |
? |
? |
Mild |
No |
+1 acceptor splice |
Liu et al (2002) |
Mar-02 |
| 24 |
Intron |
AG>AA |
- - |
2 |
117 |
Moderate |
No |
-1 IVS24 acceptor splice excises exon 25 |
Gau et al (2003, 2006) |
Aug-04 |
| 25 |
2223 |
GTG>ATG |
Val Met |
? |
? |
? |
? |
+1 Intr24 acceptor splice site |
Antonarakis et al (unpublished) |
Dec-94 |
| 25 |
Intron |
AAG/gt>AAG/ct |
- - |
12 |
? |
Mild |
No |
IVS25+1 donor splice site |
Silva Pinto et al (unpublished) |
Aug-04 |
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FVIII:C and/or FVIII:Ag values in this table which do not appear in the
indicated publications have been personally communicated. |
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