Factor XI Variant Database

c.764G>A

p.Cys255Tyr (Legacy AA No. 237)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Expression studies showed that although mutant protein was synthesised in BHK transfected cells, it was not secreted. The medium of cells transfected with recombinant Cys255Tyr contained 3% of factor XI antigen secreted by normal cells but no demonstrable factor XI activity. The Cys255Tyr mutation disrupts the C226-C255 bond in Ap3. Zivelin et al 2002

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
4	13	M	French Basque/Jewish	<1		Compound heterozygote		Severe	No bleeding after tonsillectomy following pl asma treatment	Zivelin et al 2002
103	10	M		<1			c.403G>T (p.Glu135*)	Severe	No bleeding after testicular surgery following plasma treatment	Zivelin et al 2002

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.783G>C

p.Glu261Asp (Legacy AA No. 243)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

15

Allele Number *:

251328

Allele Frequency *:

0.000060

Variant Comments & Reference:

Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
204	20	M	French	30	28	Heterozygote		Not Reported	Easy Bruising	Quelin et al 2005
205		M	French	30		Compound heterozygote	c.1613C>T (p.Pro538Leu)	Not Reported		Quelin et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.788G>A

p.Gly263Glu (Legacy AA No. 245)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Hill et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
173	27	F		31	26	Heterozygote		Mild	Easy bruising, has had thrombosis, no bleeding history	Hill et al 2005
174	52	F		61		Heterozygote		Mild	Asymptomatic	Hill et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.797G>A

p.Ser266Asn (Legacy AA No. 248)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

II

Allele Count *:

71

Allele Number *:

282734

Allele Frequency *:

0.000251

Variant Comments & Reference:

Mutant protein activates FXI normally in purified protein system and has normal activity, however activation of mutant protein by thrombin in presence of activated platelets is slower than normal. The mutation is associated with reduction in affinity for platelets. Sun et al 2001

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
15	9	M	African American	42	70	Compound heterozygote		Mild	History of excessive bleeding after dental procedures and frequent epistaxis. Required plasma transfusions.	Martincic et al 1998
16		F	African American	67	80	Heterozygote		Not Reported	History of abnormal hemostastis with bleeding after dental procedures, frequent epistaxis and heavy bleeding after childbirth.	Martincic et al 1998

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.801A>G

p.Thr267= (Legacy AA No. 249)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

A>G

Variant Effect:

Silent

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

41844

Allele Number *:

282688

Allele Frequency *:

0.148022

Variant Comments & Reference:

Frequency in a random sample of normal volunteers is 19%, making this variant a polymorphism. Martincic et al 1998, Ventura et al 2000

Patient Information: Show

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Silent) variant.

c.802C>T

p.Arg268Cys (Legacy AA No. 250)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

5

Phenotype:

U

Allele Count *:

21

Allele Number *:

282758

Allele Frequency *:

0.000074

Variant Comments & Reference:

Bolton-Maggs et al 2003 (Abstract), Esteban et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	Inheritance	Severity	Reference
44					Heterozygote	Not Reported	Bolton-Maggs et al 2003 Abstract
45					Homozygote	Severe	Bolton-Maggs et al 2003 Abstract
238			UK Population	8	Homozygote	Not Reported	Mitchell et al 2006
239			UK Population	53	Heterozygote	Not Reported	Mitchell et al 2006
603	69	F	Spanish	35	Heterozygote	Not Reported	Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.803G>A

p.Arg268His (Legacy AA No. 250)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

7

Allele Number *:

282734

Allele Frequency *:

0.000025

Variant Comments & Reference:

Homologue scanning mutagenesis studies of conformationally constrained synthetic peptides identified amino acid residues Arg268 (and Lys273) as being important for binding of FXI to platelets. Amino acid change at Arg268His is likely to cause disruption to normal platelet binding (but not as much as would Arg268Cys). Ho et al 2000, Duncan et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
356	9	F		24		Compound heterozygote		Not Reported	Patient has a bleeding Hx.	Duncan et al 2008
425	9	F	Australian	24		Compound heterozygote	c.717insT	Not Reported	Patient has a bleeding Hx.	Duncan et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.809A>T

p.Lys270Ile (Legacy AA No. 252)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

A>T

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

148

Allele Number *:

282756

Allele Frequency *:

0.000523

Variant Comments & Reference:

Expression of mutant proteins in stably transfected cells showed a 73% reduction, but expression of the mutant protein in cell lysates was similar to normal - suggests mutant protein was synthesised but secretion was reduced. Dai et al 2004

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
60			North European Caucasian	4		Compound heterozygote	c.438C>A (p.Cys146*)	Severe	No active bleeding problems following laporoscopic sterilization.	Dai et al 2004
240			UK Population	4		Compound heterozygote	c.438C>A (p.Cys146*)	Not Reported		Mitchell et al 2006
435	46	F	Czech	4	2	Compound heterozygote	c.218+2T>A	Not Reported		Castaman et al 2008
436	85	F	Australian	52		Compound heterozygote	c.976C>T (p.Arg326Cys)	Not Reported	Median aPTT time: 46 seconds.	Duncan et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.829G>A

p.Gly277Ser (Legacy AA No. 259)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Unpublished Data

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
507				44	34	Heterozygote		Not Reported		Unpublished Data

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.841C>T

p.Gln281* (Legacy AA No. 263)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

22

Phenotype:

I

Allele Count *:

23

Allele Number *:

282772

Allele Frequency *:

0.000081

Variant Comments & Reference:

Saunders et al 2005, Shao et al 2016, Asselta et al 2017, Zhang et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
62	17	F	Chinese	45		Heterozygote		Mild	No history of abnormal bleeding.	Au et al 2003
64	56	F	Chinese	1		Compound heterozygote	c.1107C>A (p.Tyr369*)	Severe	Patient initially seen with prolonged bleeding after tooth extraction but there was no previous history of menorrhagia or abnormal bleeding.	Au et al 2003
65	42	F	Japanese	<1	Undetectable	Homozygote		Severe	No history of excessive bleeding and patient had given birth without bleeding complications.	Sato et al 2000
115	20	F	Chinese	49		Heterozygote		Mild		Au et al 2003
119		F	Japanese	55		Heterozygote		Mild		Sato et al 2000
120		M	Japanese	40		Heterozygote		Mild		Sato et al 2000
121		F	Japanese	61		Heterozygote		Mild		Sato et al 2000
122		M	Japanese	<1		Homozygote		Severe		Sato et al 2000
123		M	Japanese	40		Heterozygote		Mild		Sato et al 2000
150	29	M	Japanese	<1	<1	Compound heterozygote		Severe	Spontaneous bleeding and/or heavy bleeding	Kawaguchi et al 2000
399	25	F	Chinese	260	3	Compound heterozygote		Not Reported		Wang et al 2009
615	30	F		1	<1	Homozygote		Not Reported	Peptic ulcer with bleeding	Lin et al 2020
618	26	F	Chinese	3		Compound heterozygote	c.1107C>T (p.Tyr369=)	Not Reported	Bleeding upon tooth extraction	Shao et al 2016
619	41	F	Chinese	4		Compound heterozygote	c.1778C>T (p.Thr593Met)	Not Reported	Bleeding following injury/surgery and postpartum hemorrhage	Shao et al 2016
625	22	F	Chinese	<1		Compound heterozygote	c.326-1G>A	Not Reported	Epistaxis and easy bruising	Shao et al 2016
626	33	M	Chinese	2		Compound heterozygote	c.1107C>T (p.Tyr369=)	Not Reported	Bleeding following injury/surgery	Shao et al 2016
651	43	F	Taiwanese	1		Homozygote		Not Reported	Easy bruising, bleeding after dental extraction and postoperative bleeding (Grade II bleeding)	Lin et al 2020
655	13	M	Taiwanese	7		Compound heterozygote	c.434A>G (p.His145Arg)	Not Reported	Easy bruising (Grade II bleeding)	Lin et al 2020
656	38	F	Taiwanese	<1		Homozygote		Not Reported	Bleeding after dental extraction (Grade II bleeding)	Lin et al 2020
657	61	M		2	<1	Compound heterozygote	c.1107C>A (p.Tyr369*)	Not Reported	No bleeding	Lin et al 2020
679	4	M		<1		Compound heterozygote	c.738G>A (p.Trp246*)	Severe	Bruising	Zhang et al 2020
687	30	F		6		Homozygote		Severe	Bruising	Zhang et al 2020

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Nonsense) variant.

c.861C>T

p.Ile287= (Legacy AA No. 269)

Variant Type:

Point

Domain:

Linker

Codon Change:

C>T

Variant Effect:

Silent

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

281

Allele Number *:

282734

Allele Frequency *:

0.000994

Variant Comments & Reference:

Polymorphism. Cargill et al 1999

Patient Information: Show

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Silent) variant.

c.865G>C

p.Val289Leu (Legacy AA No. 271)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

1

Allele Number *:

251340

Allele Frequency *:

0.000004

Variant Comments & Reference:

As Val289 is the last codon of exon 8, located at its 3' splice donor junction, a mutation at this consensus splice sequence is predicted to abolish the physiological donor splice site for exon 8, resulting in an abnormal FXI transcript. Jayandharan et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
141	9	M	Indian	2		Compound heterozygote	c.1432G>A (p.Gly478Arg)	Not Reported	Post op bleeding only	Jayandharan et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.901T>C

p.Phe301Leu (Legacy AA No. 283)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

22

Phenotype:

I

Allele Count *:

297

Allele Number *:

282824

Allele Frequency *:

0.001050

Variant Comments & Reference:

Jewish Type III. Mutant protein was secreted at reduced levels (8%) compared to wild type. Northern blot analysis demonstrated that wild type and mutant protein generated similar amounts of mRNA. Meijers et al 1992, Kravtsov et al 2004, Tiscia et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
17	67	M	Jewish	<3	<5	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	History of postoperative and posttraumatic bleeding requiring multiple transfusions of fresh frozen plasma.	Martincic et al 1998
18	42	F	Caucasian	4		Compound heterozygote	c.1026dupG	Severe	Mild bleeding after dental surgery	Dossenbach-Glaninger et al 2001
76	36	M	Ashkenazi Jewish	<10	<10	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	Trivial - few mild but insignificant bleeding episodes.	Asakai et al 1989
77	50	F	Ashkenazi Jewish	<10	<10	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	None	Asakai et al 1989
79	55	F	Ashkenazi Jewish	<10	<10	Homozygote		Severe	Mild - few episodes of mild but significant bleeding	Asakai et al 1989
80	48	F	Ashkenazi Jewish	<10	<10	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	Moderate - recurrent episodes of moderately severe bleeding, sometimes requiring a blood transfusion.	Asakai et al 1989
81	64	F	Ashkenazi Jewish	<10	<10	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	Moderate - recurrent episodes of moderately severe bleeding, sometimes requiring a blood transfusion.	Asakai et al 1989
112		F	Caucasian	76		Heterozygote		Mild	Mild bleeding during and after abdominal surgery	Dossenbach-Glaninger et al 2001
113		M	Caucasian	87		Heterozygote		Mild	No evidence of abnormal bleeding	Dossenbach-Glaninger et al 2001
283	53	F	Italian	2	6	Compound heterozygote		Not Reported	Menorrhagia. Minor bleeding not requiring substitutive treatment	Castaman et al 2008
444				6		Compound heterozygote	c.403G>T (p.Glu135*)	Not Reported		Saunders et al 2009
447					3	Compound heterozygote	c.403G>T (p.Glu135*)	Not Reported		Saunders et al 2009
453				35		Heterozygote		Not Reported		Saunders et al 2009
454				7		Homozygote		Not Reported		Saunders et al 2009
455				48		Heterozygote		Not Reported		Saunders et al 2009
459	33	F	Ashkenazi Jewish	9	9	Compound heterozygote	c.1021G>A (p.Glu341Lys)	Not Reported	Epistaxis	Zucker et al 2007
477	40	F	Czech	2	2	Compound heterozygote	c.1288G>A (p.Ala430Thr)	Not Reported	Epistaxis, post-operative bleeding and bleeding following tooth extraction. Patient also suffers from menorrhagia and experienced postpartum bleeding.	Castaman et al 2008
490		F		1	<1	Compound heterozygote	c.1489C>T (p.Arg497*)	Not Reported	No bleeding following dental extraction. Bleeding following delivery - no therapy. Easy bruising.	Quelin et al 2009
544	19	F	Italian	4		Compound heterozygote	c.595+3A>G	Not Reported	Asymptomatic	Tiscia et al 2017
545	54	M	Italian	51		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
547	12	F	Italian	6		Compound heterozygote	c.1556G>A (p.Trp519*)	Not Reported	Surgery-related bleeding	Tiscia et al 2017
549	36	F	Italian	85		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.922A>T

p.Ile308Phe (Legacy AA No. 290)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

A>T

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Polymorphism. Cargill et al 1999

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.923T>C

p.Ile308Thr (Legacy AA No. 290)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

18

Allele Number *:

251388

Allele Frequency *:

0.000072

Variant Comments & Reference:

Polymorphism. Hill et al 2005

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.938G>T

p.Ser313Ile (Legacy AA No. 295)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

8

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Variant predicted to disrupt hydrogen-bond formation, altering protein structure and function. Wang et al 2019, Xia et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
640	32	F	Chinese	2	5.4	Compound heterozygote	c.738G>A (p.Trp246*)	Not Reported	Heavy menorrhagia and delayed wound healing	Wang et al 2019
641		M	Chinese	41	47.4	Heterozygote		Not Reported	No bleeding disorders	Wang et al 2019
643		F	Chinese	58	63.1	Heterozygote		Not Reported	No bleeding disorders	Wang et al 2019
646		M	Chinese	57	59.8	Heterozygote		Not Reported	No bleeding disorders	Wang et al 2019
667		F				Compound heterozygote	c.738G>A (p.Trp246*)	Not Reported	Reduced FXI activity and antigen levels to 10% and 15% of normal, respectively.	Xia et al 2020
668		F				Compound heterozygote	c.738G>A (p.Trp246*)	Not Reported	Reduced FXI activity and antigen levels to 2% and 11.5% of normal, respectively.	Xia et al 2020
672		M				Heterozygote		Not Reported		Xia et al 2020
673		F				Heterozygote		Not Reported		Xia et al 2020

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.943G>A

p.Glu315Lys (Legacy AA No. 297)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

11

Phenotype:

I

Allele Count *:

8

Allele Number *:

282756

Allele Frequency *:

0.000028

Variant Comments & Reference:

Expression of Glu315Lys in BHK cells revealed impaired secretion (4.5% of wild-type FXI) despite the presence of 70% of wild-type FXI antigen in cell lysate, which was shown to be a dimer by western blot analysis. Zucker et al 2007, Tiscia et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
152				40		Heterozygote		Not Reported	No bleeding tendency	Mathonet et al 1999 (Abstract)
194	57	M	French	38	39	Heterozygote		Not Reported	Epistaxis	Quelin et al 2006
195	25	F	French	40		Heterozygote		Not Reported		Quelin et al 2006
210	31	M	French	40	52	Heterozygote		Not Reported		Quelin et al 2005
430				4		Compound heterozygote	c.943G>T (p.Glu315*)	Not Reported	No bleeding tendency	Hopmeier et al 2004
495	24	F	Belgic	<2	<5	Compound heterozygote	c.1634G>A (p.Cys545Tyr)	Severe	Bleeding after tooth extraction.	Zucker et al 2007
551	31	F	Italian	7		Compound heterozygote	c.1556G>A (p.Trp519*)	Not Reported	Vaginal bleeding during pregnancy	Tiscia et al 2017
553	53	F	Italian	39		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
554	29	F	Italian	29		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
561	3	F	Italian	34		Compound heterozygote	c.1682G>A (p.Ala561Asp)	Not Reported	Asymptomatic	Tiscia et al 2017
562	30	F	Italian	36		Compound heterozygote	c.1682G>A (p.Ala561Asp)	Not Reported	Asymptomatic	Tiscia et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.943G>T

p.Glu315* (Legacy AA No. 297)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>T

Variant Effect:

Nonsense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Hopmeier et al 2004

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
430				4		Compound heterozygote	c.943G>A (p.Glu315Lys)	Not Reported	No bleeding tendency	Hopmeier et al 2004

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Nonsense) variant.

c.959T>C

p.Leu320Pro (Legacy AA No. 302)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Amount of mutant protein secreted from cells in vitro is reduced. Leu320 occurs adjacent to Cys321, which forms a disulfide bond with Cys327. Structural predictions indicate that the substitution of Pro for Leu320 causes the helical conformation at Cys317, Gln318, and Lys319 of the normal protein to be changed to turn and coil conformations. These changes in protein conformation might prevent the formation of the Cys321- Cys327 disulfide bond, altering the structure of the fourth apple domain. Pugh et al 1995

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.965C>T

p.Thr322Ile (Legacy AA No. 304)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

I

Allele Count *:

4

Allele Number *:

251374

Allele Frequency *:

0.000016

Variant Comments & Reference:

Thr322Ile was introduced into factor XI cDNA by site directed mutagenesis and cloned into pEXV-3. Amount of mutant protein secreted from cells in vitro is reduced. Pugh et al 1995

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Severity	Comments	Reference
211	36	F	French	11	26	Homozygote	Not Reported	Epistaxis, Menorrhagia and bleeding after tonsillectomay, dental extraction and d elivery	Quelin et al 2005
242			UK Population	51		Heterozygote	Not Reported		Mitchell et al 2006
602	42	M	Spanish	47		Heterozygote	Not Reported		Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.973G>T

p.Val325Phe (Legacy AA No. 307)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

U

Allele Count *:

2

Allele Number *:

251386

Allele Frequency *:

0.000008

Variant Comments & Reference:

Val325Phe is located buried at the surface of the Ap4 domain, and lies at the interface between the Ap1 and Ap4 domains, thus this mutation may disrupt the packing between the Ap domains. Saunders et al 2009

Patient Information: Show

Patient_ID	FXI:C%	Inheritance	Severity	Reference
432	55	Heterozygote	Not Reported	Saunders et al 2009
433	52	Heterozygote	Not Reported	Saunders et al 2009
434	50	Heterozygote	Not Reported	Saunders et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

Unspecified (R326H)

p.Arg326His (Legacy AA No. 308)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Shao et al 2016

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.976C>T

p.Arg326Cys (Legacy AA No. 308)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

6

Allele Number *:

251384

Allele Frequency *:

0.000024

Variant Comments & Reference:

Introduction of a Cys residue may disrupt disulphide bridge formation. Arg326 lies close to the part of the Ap4 domain responsible for extensive non-covalent interactions between the FXI monomers. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
19				41	33	Heterozygote		Mild	History of easy bruising.	Mitchell et al 1999
243			UK Population	43	33	Heterozygote		Not Reported		Mitchell et al 2006
436	85	F	Australian	52		Compound heterozygote	c.809A>T (p.Lys270Ile)	Not Reported	Median aPTT time: 46 seconds.	Duncan et al 2008
437				36		Heterozygote		Not Reported		Saunders et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.981C>A

p.Cys327* (Legacy AA No. 309)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

C>A

Variant Effect:

Nonsense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

1

Allele Number *:

251406

Allele Frequency *:

0.000004

Variant Comments & Reference:

Cys327* occurs in the Ap4 domain, with disruption of the Cys321-Cys327 pairing in the inner loop. Castaman et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
457	61	M	Italian	<0.5	4	Compound heterozygote	c.403G>T (p.Glu135*)	Severe		Castaman et al 2008

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Nonsense) variant.

c.992C>T

p.Thr331Ile (Legacy AA No. 313)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Interestingly, this mutation is similar to the Thr51Ile conversion but occurs in Ap4. This Thr residue, Thr331, which is laid in the extended strand positioned after alpha-helix, is conserved in positions 60, 150, 240 and 331 of Apple 1, 2, 3 and 4 domains, respectively. The major role of Apple 4 is to mediate dimer formation of two identical polypeptide chains and the Thr331Ile change may distort the conformation of the Apple 4 domain and interfere with its function. Fard-Esfahani et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
458	45	M	Iranian	<1		Homozygote		Severe	Moderate haemorrhage following oral surgery. Consanguineous parents.	Fard-Esfahani et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1016G>T

p.Cys339Phe (Legacy AA No. 321)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

566

Allele Number *:

282858

Allele Frequency *:

0.002001

Variant Comments & Reference:

Polymorphism. Cys339 pairs with other Cys339 of Ap4 at dimerisation - however it is not required for dimerisation. SDS-PAGE analysis revealed only monomer of FXI present, but mutant protein expressed in BHK cells and normal FXI secretion and activity was present. Meijers 1992, Zivelin et al 2002

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1021G>A

p.Glu341Lys (Legacy AA No. 323)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

6

Phenotype:

I

Allele Count *:

4

Allele Number *:

251454

Allele Frequency *:

0.000016

Variant Comments & Reference:

Glu341 lies close to the part of the Ap4 domain responsible for extensive non-covalent interactions between the FXI monomers. Amount of mutant protein secreted from cells in vitro is reduced. Pugh et al 1995, Saunders et al 2009, Zhang et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
134			Chinese			Heterozygote		Not Reported		Wu et al 2004 (Abstract)
220			UK Population	9		Compound heterozygote	c.325G>A (p.Ala109Thr)	Not Reported		Mitchell et al 2006
459	33	F	Ashkenazi Jewish	9	9	Compound heterozygote	c.901T>C (p.Phe301Leu)	Not Reported	Epistaxis	Zucker et al 2007
623	50	M	Chinese	3		Compound heterozygote	c.1253G>T (p.Gly418Val)	Not Reported	Easy bruising and bleeding following injury/surgery	Shao et al 2016
682	39	M		6.4		Compound heterozygote	c.55G>A	Severe	Asymptomatic	Zhang et al 2020
684	26	F		<1		Compound heterozygote	c.1556G>A (p.Trp519*)	Severe	Intra-articular bleeding	Zhang et al 2020

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1026G>T

p.Gly342= (Legacy AA No. 324)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>T

Variant Effect:

Silent

No. of Patients Reported:

3

Phenotype:

I

Allele Count *:

1

Allele Number *:

251462

Allele Frequency *:

0.000004

Variant Comments & Reference:

This alteration is predicted to affect pre-mRNA splicing and is a synonymous codon change (GGG_GGT) at codon G342 in exon 9. Variant creates a new donor splice site and introduces a premature stop codon at codon 348. Variant is believed to be a polymorphism. Ventura et al 2000

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
54		F	Portuguese	1	5	Compound heterozygote	c.1608G>C (p.Lys536Asn)	Severe	Excessive bleeding after dental extraction. Menorrhagia.	Ventura et al 2000
55		F	Portuguese	1	12	Compound heterozygote	c.1608G>C (p.Lys536Asn)	Severe	Non-bleeder.	Ventura et al 2000
470	50	F	Portugese	2		Compound heterozygote	c.1247G>A (p.Cys416Tyr)	Not Reported	No bleeding Hx.	Zucker et al 2007

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Silent) variant.

c.1033A>T

p.Lys345* (Legacy AA No. 327)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

A>T

Variant Effect:

Nonsense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Lin et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
658	64	M		1	<1	Compound heterozygote		Not Reported	No bleeding	Lin et al 2020

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Nonsense) variant.

c.1060G>A

p.Gly354Arg (Legacy AA No. 336)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

3

Allele Number *:

251410

Allele Frequency *:

0.000012

Variant Comments & Reference:

Saunders et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
29	28	M	Lebanese	<1	3	Compound heterozygote	c.682C>T (p.Arg228*)	Severe	No excessive bleeding after dental extractions and u pper limb fracture.	Quelin et al 2004
381			Non-Jewish			Compound heterozygote		Not Reported		Castaman et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1077A>G

p.Ile359Met (Legacy AA No. 341)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

A>G

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

1

Allele Number *:

251412

Allele Frequency *:

0.000004

Variant Comments & Reference:

Ile359 is one of several residues involved in the non-covalent interactions between two Ap4 domains in a FXI dimer. Saunders et al 2009

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1079T>C

p.Leu360Pro (Legacy AA No. 342)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

This non-conservative change in the surface region of the Apple 4 domain, where active FXII attaches, converts hydrophobic Leu to Pro. Substitution may lead to changes in the contact surface conformation, preventing appropriate activation of FXI. Fard-Esfahani et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
460	17	M	Iranian	<1		Homozygote		Severe	Moderate haemorrhage following abdominal surgery	Fard-Esfahani et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1084G>A

p.Gly362Arg (Legacy AA No. 344)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

22

Allele Number *:

282750

Allele Frequency *:

0.000078

Variant Comments & Reference:

Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
246			UK Population	38		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1102G>A

p.Gly368Arg (Legacy AA No. 350)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

The Gly368Arg mutant is thought not to be secreted as the patient in which the mutation was found shows a parallel defect of both FXI:C and FXI:Ag levels. Quelin et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
461		M		<1	<1	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	Post traumatic bleeding following surgery for a maxillary fracture. Bleeding also occurred under fresh frozen plasma (FFP) prophylactic infusion for surgical material removal. Two other uncomplicated surgical procedures were performed in this patient under prophylactic FFP cover.	Quelin et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1103G>C

p.Gly368Ala (Legacy AA No. 350)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

II

Allele Count *:

1

Allele Number *:

251366

Allele Frequency *:

0.000004

Variant Comments & Reference:

Decreases FXI dimerisation. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
31	85	F	Nantes	1	20	Homozygote	c.1797T>A (p.Cys599*)	Severe	Patient suffered epistaxis. Also bled after dental extraction without treatment, treated after procedure with fresh frozen plasma. Showed brusing after delivery without treatment.	Quelin et al 2004

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1103G>A

p.Gly368Glu (Legacy AA No. 350)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

3

Allele Number *:

251366

Allele Frequency *:

0.000012

Variant Comments & Reference:

FXI-Gly368Glu (FXI-Nagoya II), with a more profound defect in dimerisation than FXI-Phe301Leu, would not be expected to influence secretion of wild-type protein appreciably, as was observed in co-transfection experiments. Northern blot analysis demonstrated that wild type and mutant protein generated similar amounts of mRNA. Kravtsov et al 2004, Yang et al 2021

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	Inheritance	Other Variants	Severity	Comments	Reference
620	6	F	Chinese	1	Compound heterozygote	c.1136-4delGTTG	Not Reported	Epistaxis	Shao et al 2016
674		F			Compound heterozygote	c.1556G>A (p.Trp519*)	Not Reported	Reduced FXI activity and antigen levels to 1% and 1.3% of normal, respectively.	Yang et al 2021
675		F			Heterozygote		Not Reported		Yang et al 2021
676		M			Heterozygote		Not Reported		Yang et al 2021

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1106A>C

p.Tyr369Ser (Legacy AA No. 351)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

A>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Tyr369 is highly conserved in the FXI amino acid sequences of related proteases of different species, indicating the importance of this residue to the structure of Ap4 domain in FXIa. Ap4 is important for the dimerisation of FXIa. A missense substitution at the adjoining residue Gly368Glu (factor XI Nagoya II) has been demonstrated (by expression studies) to have a profound effect on FXIa dimerization. It is possible that Tyr369Ser could have a similar effect on FXIa dimerisation. Kravtsov et al 2004, Jayandharan et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
143	6	F	Indian	<1		Homozygote		Severe	None	Jayandharan et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1107C>A

p.Tyr369* (Legacy AA No. 351)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

C>A

Variant Effect:

Nonsense

No. of Patients Reported:

9

Phenotype:

U

Allele Count *:

10

Allele Number *:

282746

Allele Frequency *:

0.000035

Variant Comments & Reference:

Saunders et al 2005, Zhang et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
63	10	F	Chinese	53		Heterozygote		Mild	No history of abnormal bleeding.	Au et al 2003
64	56	F	Chinese	1		Compound heterozygote	c.841C>T (p.Gln281*)	Severe	Patient initially seen with prolonged bleeding after tooth extraction but there was no previous history of menorrhagia or abnormal bleeding.	Au et al 2003
116	18	F	Chinese	59		Heterozygote		Mild		Au et al 2003
649	29	M	Taiwanese	<1		Compound heterozygote	c.730C>T (p.Gln244*)	Not Reported	Bleeding after dental extraction and hematuria (Grade II bleeding)	Lin et al 2020
652	58	M	Taiwanese	<1		Compound heterozygote	c.738G>A (p.Trp246*)	Not Reported	Gastrointestinal bleeding (Grade III bleeding)	Lin et al 2020
653	69	F	Taiwanese	<1		Homozygote		Not Reported	Asymptomatic	Lin et al 2020
657	61	M		2	<1	Compound heterozygote	c.841C>T (p.Gln281*)	Not Reported	No bleeding	Lin et al 2020
659	7	M		1	<1	Compound heterozygote	c.326-1G>A	Not Reported	Epistaxis	Lin et al 2020
689	49	M		1.1		Homozygote		Severe	Asymptomatic	Zhang et al 2020

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Nonsense) variant.

c.1107C>T

p.Tyr369= (Legacy AA No. 351)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

C>T

Variant Effect:

Silent

No. of Patients Reported:

3

Phenotype:

U

Allele Count *:

1

Allele Number *:

251352

Allele Frequency *:

0.000004

Variant Comments & Reference:

Lin et al 2020, Shao et al 2016

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
618	26	F	Chinese	3		Compound heterozygote	c.841C>T (p.Gln281*)	Not Reported	Bleeding upon tooth extraction	Shao et al 2016
626	33	M	Chinese	2		Compound heterozygote	c.841C>T (p.Gln281*)	Not Reported	Bleeding following injury/surgery	Shao et al 2016
647	54	F	Taiwanese	1	4.1	Compound heterozygote	c.1322delT	Not Reported	Easy bruising, menorrhagia and postpartum hemorrhage (Grade II bleeding)	Lin et al 2020

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Silent) variant.

c.1118T>C

p.Leu373Ser (Legacy AA No. 355)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

9

Allele Number *:

282678

Allele Frequency *:

0.000032

Variant Comments & Reference:

May disrupt a neighbouring disulphide bridge. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
247			UK Population	67		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1120T>C

p.Cys374Arg (Legacy AA No. 356)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Disrupts Cys291-Cys374 disulphide bridge. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
248			UK Population	40		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1135+5G>A

(Legacy AA No. 360)

Variant Type:

Point

Domain:

Intronic

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

6

Allele Number *:

281714

Allele Frequency *:

0.000021

Variant Comments & Reference:

Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
249			UK Population	73		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1165G>A

p.Val389Ile (Legacy AA No. 371)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

II

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Residue Val389 is located one residue following the cleavage site of FXI (P2' position, according to the convention of numbering position around the scissile bond), thus is part of the activation loop. FXI antigen levels, measured in both conditioned media and lysates of cells expressing the mutant protein (in either the heterozygous or homozygous state), were not significantly different from those measured in wild-type samples. FXI specific activity was measured in conditioned media. The specific activity of the FXI Val389Ile protein was significantly reduced when compared with the wildtype one (30% and 80% for the heterozygous and the homozygous conditions, respectively). Given the proximity of Val389 to the FXI activation site, a possible interference on FXI activation was hypothesized and this mutation was found to be associated with a defect both in FXI activation (slower than normal), and in FIX activation (slightly delayed), thus supporting the role of residues neighboring the active site in influencing and stabilizing the enzyme active state. Bozzao et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
464	26	M	Italian	34	102	Heterozygote		Not Reported	Asymptomatic. Appendectomy, adenoidectomy and right knee arthroscopy had been without mishap. Patient's mother, born 1949, also had reduced FXI:C (43%) associated with normal FXI:Ag (132%), whereas the father, born 1947, had both functional and antigen FXI levels within normal range (96 and 134%, respectively).Mother had same Val371Ile in heterozygous state. Both parents were asymptomatic.	Bozzao et al 2007

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1169G>C

p.Gly390Ala (Legacy AA No. 372)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Karimi et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
465	9	F	Iranian	35		Compound heterozygote	c.1693G>A (p.Glu565Lys)	Not Reported	Haematuria and epistaxis requiring FFP for treatment and prophylaxis. No parent consanguinity; FXI activity of parents: father 46%, mother 54%.	Karimi et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1178C>T

p.Ala393Val (Legacy AA No. 375)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

II

Allele Count *:

2

Allele Number *:

251490

Allele Frequency *:

0.000008

Variant Comments & Reference:

Ala393Val is exposed in the SP domain on the opposite side of where the His431-Asp480-Ser575 catalytic triad at the active site is located; however, its effect is not clear from the FXI structure. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
467				35	69	Heterozygote		Not Reported		Saunders et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1186C>T

p.Arg396Cys (Legacy AA No. 378)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

II

Allele Count *:

5

Allele Number *:

251486

Allele Frequency *:

0.000020

Variant Comments & Reference:

Expression studies indicate that this is a causative mutation (rather than a benign polymorphism -Germanos-Haddad et al 2003). FXI antigen assays confirm that FXI-Cys396 is secreted. FXI activity assays show FXI-Cys396 to have minimal activity, demonstrating that it is functionally inactive in an APTT-based assay. If, as is suggested in the Germanos-Haddad abstract, Arg396Cys is identified in the 'normal' lebanese population, thus leading to it being misassigned as a polymorphism, then it is possible that it is a common founder mutation. Mitchell et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
245			UK Population	61	83	Heterozygote		Not Reported		Mitchell et al 2006
468		F		44		Heterozygote		Not Reported	Patient bleeds++, 'Slow wound healing' and menorrhagia.	Mitchell et al 2007

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1191T>C

p.Gly397= (Legacy AA No. 379)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>C

Variant Effect:

Silent

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

42597

Allele Number *:

282848

Allele Frequency *:

0.150600

Variant Comments & Reference:

Frequency in a random sample of normal volunteers is 18%, making this variant a polymorphism. Martincic et al 1998, Wiewel-Verschueren et al 2017

Patient Information: Show

Structural Interpretation:

Structural analysis cannot be performed on this (Point | Silent) variant.

c.1195T>C

p.Trp399Arg (Legacy AA No. 381)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Polymorphism. Unpublished Data

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

C.1196G>T

p.Trp399Leu (Legacy AA No. 381)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Variant likely leads to altered protein secretion. It is unlikely to have an effect on the structure of the catalytic domain as both Trp and Leu are hydrophobic amino acids. Quelin et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
389		F		35	40	Heterozygote		Not Reported	Pt presented with post-operative menorrhagia after a termination of pregnancy without prophylaxis. After that, multiple surgical procedures were performed without comlpication under afibrinolytic prophylaxis.	Quelin et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1199C>T

p.Pro400Leu (Legacy AA No. 382)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

I

Allele Count *:

2

Allele Number *:

251476

Allele Frequency *:

0.000008

Variant Comments & Reference:

Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Reference
151			European	<1		Compound heterozygote	c.408C>A (p.Cys136*)	Severe	Bolton-Maggs et al 1999 Abstract
209	58	M	French	<1	<1	Compound heterozygote	c.166T>C (p.Cys56Arg)	Severe	Quelin et al 2005
226			UK Population	<1		Compound heterozygote	c.408C>A (p.Cys136*)	Severe	Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

Factor XI Gene (F11)

Variant Database

Data Export Options:

UNIQUE (Without Patient Data) : EXCEL/CSV TABULAR MULTIPLE (With Patient Data) : EXCEL/CSV TABULAR

Full List of Variants: 272 unique variants retrieved (displaying 50 entries per page). Scroll down to navigate to the next page(s).

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UNIQUE (Without Patient Data) :

EXCEL/CSV

TABULAR

MULTIPLE (With Patient Data) :

EXCEL/CSV

TABULAR