Factor XI Variant Database

c.1202G>A

p.Trp401* (Legacy AA No. 383)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Nonsense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

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
132		F	Chinese			Compound heterozygote	c.738G>A (p.Trp246*)	Not Reported		Wu et al 2003 (Abstract)

Structural Interpretation:

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

Unspecified (V403M)

p.Val403Met (Legacy AA No. 385)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Heterodimer trapping. Duga & Salomon 2013

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1211C>A

p.Thr404Asn (Legacy AA No. 386)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>A

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Saunders et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Severity	Comments	Reference
32	8	F	Arab	2	Decreased	Homozygote	Severe	No history of abnormal bleeding and no surgery. Received fresh frozen plasma at age 8 for release of tethered spinal cord without unusual bleeding.	Wistinghausen et al 1997
33		M	Arab	2	Decreased	Homozygote	Severe	Minor bleeding following surgery on patients nose.	Wistinghausen et al 1997
34		F	Arab	108	Normal	Heterozygote	Mild		Wistinghausen et al 1997

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1217A>C

p.His406Pro (Legacy AA No. 388)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

A>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

His406 is not charged but is involved in two polar contacts with Arg443 on the opposite beta strand. A turn induced by Pro is likely to disrupt the beta sheet structure. de Raucourt et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
469	32	F	French	0.36	0.37	Heterozygote		Severe	No personal or familial abnormal bleeding Hx. Routine coagulation tests performed before a lipoma resection revealed an isolated partial FXI deficiency. Surgical procedure was performed with antifibrinolytic treatment without any complication.	de Raucourt et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1219A>C

p.Thr407Pro (Legacy AA No. 389)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

A>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Bolton-Maggs et al 2003 (Abstract)

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
250			UK Population	35		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1222A>C

p.Thr408Pro (Legacy AA No. 390)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

A>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

2

Allele Number *:

251474

Allele Frequency *:

0.000008

Variant Comments & Reference:

Unpublished Data

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1234C>T

p.Gln412* (Legacy AA No. 394)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Kawankar et al 2016

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
628	14	M	Indian	<1		Homozygote		Not Reported	No bleeding	Kawankar et al 2016

Structural Interpretation:

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

c.1247G>A

p.Cys416Tyr (Legacy AA No. 398)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

17

Phenotype:

I

Allele Count *:

4

Allele Number *:

251468

Allele Frequency *:

0.000016

Variant Comments & Reference:

Mutant protein is not expressed by 293 human kidney fibroblasts. Western blot shows mutant protein forms intracellular dimer. Transfections show reduced secretion of mutant protein. Has a dominant negative effect on wild type secretion. This mutation breaks the disulphide bridge between Cys416-Cys432. Gailani et al 2001 (Abstract), Kravtsov et al 2005, Saunders et al 2009, Esteban et al 2017, Colakoglu et al 2018

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
84		F	English	<1		Homozygote		Severe	Menorrhagia and excessive bleeding after appendectomy.	Gailani et al 2001 Abstract B
85			English	40		Heterozygote		Mild	No bleeding abnormalities	Gailani et al 2001 Abstract B
114			Hispanic	40		Heterozygote		Mild	No bleeding abnormalities	Gailani et al 2001 Abstract B
146	38	F		25	25	Heterozygote		Not Reported	Heavy post-partum bleeding and idiopathic hematuria.	Kravtsov et al 2005
251			UK Population	<1		Homozygote		Severe		Mitchell et al 2006
252			UK Population	58		Heterozygote		Not Reported		Mitchell et al 2006
470	50	F	Portugese	2		Compound heterozygote	c.1026G>T (p.Gly342=)	Not Reported	No bleeding Hx.	Zucker et al 2007
471	58	F	Portgugese	2		Compound heterozygote	c.1072delA	Not Reported	No Bleeding Hx.	Zucker et al 2007
472				43		Heterozygote		Not Reported		Saunders et al 2009
525	28	F	Turkish			Heterozygote		Not Reported	Asymptomatic	Colakoglu et al 2018
586	71	F	Spanish	2		Compound heterozygote	c.166T>C (p.Cys56Arg)	Not Reported		Esteban et al 2017
587	25	M	Spanish	28		Heterozygote		Not Reported		Esteban et al 2017
588	50	F	Spanish	22		Heterozygote		Not Reported		Esteban et al 2017
589	43	M	Spanish	34		Heterozygote		Not Reported		Esteban et al 2017
590	32	F	Spanish	26		Heterozygote		Not Reported		Esteban et al 2017
591	80	F	Spanish	37		Heterozygote		Not Reported		Esteban et al 2017
592	38	M	Spanish	33		Heterozygote		Not Reported		Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1252G>A

p.Gly418Ser (Legacy AA No. 400)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

1

Allele Number *:

251466

Allele Frequency *:

0.000004

Variant Comments & Reference:

Castaman et al 2007 (ISTH Abstract)

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1253G>T

p.Gly418Val (Legacy AA No. 400)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

11

Phenotype:

I

Allele Count *:

2

Allele Number *:

251466

Allele Frequency *:

0.000008

Variant Comments & Reference:

Mutant protein is not expressed in 293 kidney fibroblasts. Northern blot analysis demonstrated that wild type and mutant protein generated similar amounts of mRNA. Co-transfection with wild-type and mutant protein reduces wild-type secretion about 50% - non-secretable mutant protein monomers trap wild-type polypeptides within cells through homodimer formation, resulting in lower FXI levels in plasma. Gly418Val exerts a dominant negative effect which stems from an impaired secretion of heterodimers consisting of a normal and a mutant monomer. Gailani 2001 et al (Abstract B), Kravtsov et al 2004, Colakoglu et al 2018, Peng et al 2020, Zhang et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
35	53	M	Italian and Czechoslovakian	15	Decreased	Heterozygote		Not Reported	History of excessive bleeding after surgery and tooth extraction.	Kravtsov et al 2004
36		F	Chinese	<2		Homozygote		Severe	Frequent gingival bleeding.	Kravtsov et al 2004
86			US	15		Heterozygote		Not Reported	Bleeding after surgical or dental procedures	Gailani et al 2001 Abstract B
305	19	F	Italian	<3	10	Compound heterozygote		Severe	Bleeding after tooth extraction - minor bleeding not requiring substitutive treatment	Castaman et al 2008
427	62	M	Japanese	<3		Compound heterozygote	c.730C>T (p.Gln244*)	Severe		Okumura et al 2006
516	8	F	Turkish			Heterozygote		Not Reported	Asymptomatic	Colakoglu et al 2018
557	53	F	Italian	45		Heterozygote		Not Reported	Easy bruising and cerebellar ischemia in oral contraceptive	Tiscia et al 2017
623	50	M	Chinese	3		Compound heterozygote	c.1021G>A (p.Glu341Lys)	Not Reported	Easy bruising and bleeding following injury/surgery	Shao et al 2016
681	4	F		<1		Compound heterozygote	c.599G>C (p.Cys200Ser)	Severe	Epistaxis	Zhang et al 2020
683	30	M		18		Heterozygote		Not Reported	Bruising	Zhang et al 2020
685	60	F		13		Heterozygote		Severe	Asymptomatic	Zhang et al 2020

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1255T>G

p.Ser419Ala (Legacy AA No. 401)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>G

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Hopmeier et al 2004

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1270C>T

p.Gln424* (Legacy AA No. 406)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Saunders et al 2009, Shao et al 2016

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
253			UK Population	46		Heterozygote		Not Reported		Mitchell et al 2006
614	49	F	Chinese	<1		Homozygote		Not Reported	Easy bruising	Shao et al 2016

Structural Interpretation:

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

Unspecified (W425L)

p.Trp425Leu (Legacy AA No. 407)

Variant Type:

Point

Domain:

Serine Protease

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.1275G>C

p.Trp425Cys (Legacy AA No. 407)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

5

Allele Number *:

282812

Allele Frequency *:

0.000018

Variant Comments & Reference:

Kravtsov et al 2004, de Raucourt et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
474	7		African	0.22	0.27	Heterozygote		Severe	No personal or family Hx of bleeding.	de Raucourt et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1277T>C

p.Ile426Thr (Legacy AA No. 408)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Esteban et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
605	25	M	Spanish	28		Heterozygote		Not Reported		Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1283C>T

p.Thr428Ile (Legacy AA No. 410)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Thr428 occupies a buried position within the FXI SP domain adjacent to His431 of the active site and may perturb either the folding or the function of the SP domain. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
475				38		Heterozygote		Not Reported		Saunders et al 2009
636	28	F	Indian	25		Heterozygote		Not Reported	No bleeding	Kawankar et al 2016

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1288G>A

p.Ala430Thr (Legacy AA No. 412)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

I

Allele Count *:

20

Allele Number *:

282590

Allele Frequency *:

0.000071

Variant Comments & Reference:

Ala430 is located in an alpha helix portion. Substitution at this position with Thr is expected to disrupt the helix structure due to steric constraints from the neighbouring residues Phe433 and Tyr434. The introduction of a polar residue in place of the simple aliphatic side chain of Ala is likely to perturb the local folding of the protein. Homology modelling suggests that this substitution might impair FXI secretion by reducing the stability of the serine protease fold. de Raucourt et al 2008, Castaman et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
413	23	F	French	0.07	0.07	Compound heterozygote		Severe	Menorrhagia, gingivorrhagia and easy bruising. Dental extractions under tranexamic acid cover associated with post-procedural excessive bleeding. APTT 55 sec, Blood Group O.	de Raucourt et al 2008
476	23	F	French	0.07	0.07	Compound heterozygote	c.596C>T (p.Ala199Val)	Severe	Menorrhagia, gingivorrhagia and easy bruising. Dental extractions under tranexamic acid cover associated with post-procedural excessive bleeding. APTT 55 sec, Blood Group O.	de Raucourt et al 2008
477	40	F	Czech	2	2	Compound heterozygote	c.901T>C (p.Phe301Leu)	Not Reported	Epistaxis, post-operative bleeding and bleeding following tooth extraction. Patient also suffers from menorrhagia and experienced postpartum bleeding.	Castaman et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1288G>T

p.Ala430Ser (Legacy AA No. 412)

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:

Ala430Ser occupies a buried position within the SP domain adjacent to His431 of the active site, and may perturb either the folding or function of the SP domain. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
479				35	35	Heterozygote		Not Reported		Saunders et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1289C>T

p.Ala430Val (Legacy AA No. 412)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Homology modelling suggests that this substitution may reduce the stability of the serine protease fold, resulting in non-secretion. O'Connell et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
20		F		45	39	Heterozygote		Mild	Dental work left patient with large facial brusing and nose bleeds. Menorrhagia.	Mitchell et al 1999
478	31	F		<1	1	Compound heterozygote	31.5KbDeletion	Severe	Patient also has Alu-mediated whole gene deletion of one allele. She does not have a bleeding Hx and has had three uncomplicated deliveries.	Hill et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1327C>T

p.Arg443Cys (Legacy AA No. 425)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

7

Allele Number *:

282750

Allele Frequency *:

0.000025

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
481				46		Heterozygote		Not Reported		Mitchell et al 2006
482				31	39	Heterozygote		Not Reported		Saunders et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1334A>G

p.Tyr445Cys (Legacy AA No. 427)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

A>G

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

1

Allele Number *:

251392

Allele Frequency *:

0.000004

Variant Comments & Reference:

Expressing Tyr445Cys in BHK cells resulted in abrogation of FXI secretion despite intact dimerisation, and was associated with a reduced amount of FXI in lysed cells. Zucker et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
148			Jewish	2		Compound heterozygote	c.403G>T (p.Glu135*)	Not Reported		Zivelin et al 1999 (Abstract)
483	44	F	Ashkenazi Jewish	<1	<1	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	Menorrhagia	Zucker et al 2007

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1336A>G

p.Ser446Gly (Legacy AA No. 428)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

A>G

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

2

Allele Number *:

251392

Allele Frequency *:

0.000008

Variant Comments & Reference:

One small hydrophilic amino acid (Ser) is replaced by another small, hydrophilic amino acid (Gly). Ser446 is conserved in bovine FXI and human prekallikrein, but it is not conserved in rabbit or murine FXI. Likely to be a non-causative polymorphism. Duncan et al 2008

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1394C>G

p.Gln451Glu (Legacy AA No. 433)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>G

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Expected to lead to disruption of the catalytic domain structure of FXI molecule. Gln451 is highly conserved among humans, cattle, mice and dogs, as well as red jungle fowl, which suggests that Gln451 may be crucial for FXI activity. Gln has no charge, while Glu has a net negative charge at physiological pH. The charge change during Gln to Glu substitution may disturb the electrostatic properties of FXI, leading to abnormal activity. Ishikawa et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	Inheritance	Other Variants	Severity	Comments	Reference
484	2	M	Japanese	<1	Compound heterozygote	c.1556insG	Severe	No history of episodes of excessive bleeding.	Ishikawa et al 2007
485	4	M	Japanese	4	Compound heterozygote	c.1556insG	Not Reported	Frequent epistaxis.	Ishikawa et al 2007
486	6	F	Japanese	64	Heterozygote		Not Reported		Ishikawa et al 2007
487		M	Japanese	58	Heterozygote		Not Reported	Father of patients 484, 485 and 486. The children's mother is heterozygous for c.1556dupG mutation.	Ishikawa et al 2007

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1694T>A

p.Ile454Lys (Legacy AA No. 436)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>A

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Induces a large conformational change within the 450–460 loop. Girolami et al 2011

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1378T>G

p.Phe460Val (Legacy AA No. 442)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>G

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

1

Allele Number *:

251396

Allele Frequency *:

0.000004

Variant Comments & Reference:

Oligonucleotide probes of WT and mutant were hybridized to 50 normal individuals. Only WT hydrized - so not a polymorphism. Imanaka et al 1995

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
38	37	F	Non-Jewish	47	50	Heterozygote		Mild	History of easy bruising but excessive bleeding after wisdom teeth extraction. Menhorragia after child birth	Imanaka et al 1995

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1393G>T

p.Glu465* (Legacy AA No. 447)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>T

Variant Effect:

Nonsense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

The G to T transversion in exon 12 results in a nonsense mutation Glu465* which leads to the disruption of the catalytic domain structure of the FXI molecule. Tsukahara et al 2003

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
69	25	M	Japanese	Undetectable	Undetectable	Compound heterozygote	c.1556insG	Severe	Asymptomatic - no abnormal bleeding history.	Tsukahara et al 2003

Structural Interpretation:

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

c.1432G>A

p.Gly478Arg (Legacy AA No. 460)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

11

Phenotype:

I

Allele Count *:

26

Allele Number *:

251454

Allele Frequency *:

0.000103

Variant Comments & Reference:

Mutant protein is expressed at levels comparable to normal FXI, and mutant protein was not secreted. Bolton-Maggs et al 2003 (Abstract)

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
10				42		Heterozygote		Mild		Mitchell et al 2003
13				51		Heterozygote		Not Reported	Long history of bleeding including epistaxis and post tonsillectomy.	Alhaq et al 2000
42						Homozygote		Severe		Bolton-Maggs et al 2003 Abstract
141	9	M	Indian	2		Compound heterozygote	c.865G>C (p.Val289Leu)	Not Reported	Post op bleeding only	Jayandharan et al 2005
142	11	M	Indian	<1		Homozygote		Severe	Severe bleeding symptoms characterized by hemarthroses, easy bruising, excessive bleeding from tooth sockets and repeated episodes of bleeding from minor injurie s since childhood.	Jayandharan et al 2005
206	40	F	French	5		Homozygote		Not Reported		Quelin et al 2005
207	4	M	French	32		Heterozygote		Not Reported		Quelin et al 2005
208	2	M	French	18	13	Compound heterozygote	c.259C>A (p.Pro87Thr)	Not Reported		Quelin et al 2005
254			UK Population	<1		Homozygote		Severe		Mitchell et al 2006
408				2	2	Compound heterozygote	c.449C>T (p.Thr150Met)	Not Reported		Saunders et al 2009
635	14	M	Indian	<1		Homozygote		Not Reported	Epistaxis	Kawankar et al 2016

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1448T>C

p.Leu483Ser (Legacy AA No. 465)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Kawankar et al 2016

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
630	42	M	Indian	34		Heterozygote		Not Reported	Post traumatic joint bleed	Kawankar et al 2016

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1478C>T

p.Thr493Ile (Legacy AA No. 475)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Expression of mutant protein shows mutant is secreted poorly compared to wild type. This mutation destroys an N-linked glycosylation site. Substitution of Thr493 with Ala, Pro, Lys or Arg all abolish the site and also severely reduce level of secreted FXI:Ag. Substitution with Ser which does not abolish the site had no affect on secretion. However substitution of Asn491 with Ala which abolishes the glycosylation site also had no affect on secretion. This indicates the cause of failure to secrete FXI is not the loss of glycolsylation site. McVey et al 2005

Patient Information: Show

Patient_ID	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Severity	Comments	Reference
46					Heterozygote	Mild		Bolton-Maggs et al 2003 Abstract
164	M	Non-Jewish	39	27	Heterozygote	Mild	Asymptomatic microscopic haematuria identified at medical examination, age 14. Bleed for 2 days following tooth extraction.	McVey et al 2005
255		UK Population	46		Heterozygote	Not Reported		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1480+2T>G

(Legacy AA No. 476)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>G

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Zucker et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
489	29	F	Ashkenazi Jewish	38	20	Heterozygote		Not Reported	Patient has no bleeding Hx.

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1489C>T

p.Arg497* (Legacy AA No. 479)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

3

Allele Number *:

251402

Allele Frequency *:

0.000012

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
258			UK Population	55		Heterozygote		Not Reported		Mitchell et al 2006
490		F		1	<1	Compound heterozygote	c.901T>C (p.Phe301Leu)	Not Reported	No bleeding following dental extraction. Bleeding following delivery - no therapy. Easy bruising.	Quelin et al 2009

Structural Interpretation:

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

c.1498T>C

p.Cys500Arg (Legacy AA No. 482)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

2

Allele Number *:

251430

Allele Frequency *:

0.000008

Variant Comments & Reference:

Cys500Arg breaks the disulphide bridge between Cys500-Cys380. Saunders et al 2009

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1500C>G

p.Cys500Trp (Legacy AA No. 482)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>G

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

1

Allele Number *:

251420

Allele Frequency *:

0.000004

Variant Comments & Reference:

Cys500Trp breaks the disulphide bridge between Cys500-Cys380. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
259			UK Population	37		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1507T>C

p.Ser503Pro (Legacy AA No. 485)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Ser503Pro converts hydrophilic small sized Ser to hydrophobic, large Pro in the buried region of the SP domain. Ser503 is in the random coil area of the structure, and may cause damaging structural effects. Fard-Esfahani et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
492	12	M	Iranian	<1		Homozygote		Severe	Off-spring of consanguineous parents. Hx of moderate haemorrhage after abdominal surgery.	Fard-Esfahani et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1531T>C

p.Tyr511His (Legacy AA No. 493)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Cells transfected with mutant protein contained reduced amounts of FXI and displayed decreased secretion. Zivelin et al 2002

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
2	22	F	French Basque	2		Compound heterozygote	c.166T>C (p.Cys56Arg)	Severe	No bleeding after an open fracture	Zivelin et al 2002
97	22	F	French Basque	1		Compound heterozygote	c.166T>C (p.Cys56Arg)	Severe	No bleeding after dental extraction	Zivelin et al 2002

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1545G>T

p.Trp515Cys (Legacy AA No. 497)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Saunders et al 2009, Tiscia et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Severity	Comments	Reference
202	29	F	French	22	25	Heterozygote	Not Reported		Quelin et al 2005
558	25	F	Italian	36		Heterozygote	Not Reported	Asymptomatic	Tiscia et al 2017
559	52	M	Italian	36		Heterozygote	Not Reported	Asymptomatic	Tiscia et al 2017
560	49	F	Italian	40		Heterozygote	Not Reported	Asymptomatic	Tiscia et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1546G>A

p.Val516Met (Legacy AA No. 498)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

7

Allele Number *:

251456

Allele Frequency *:

0.000028

Variant Comments & Reference:

Val516 is highly conserved across different species. The Val516Met mutation generates an ectopic Met residue close to the disulphide bond between C514 and C581. Bioinformatics studies using surface mapping of the evolutionary conservation level revealed that Val498 is a functionally important residue. Kwon et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
493				1		Compound heterozygote	c.1560dupG	Not Reported	Clinically, the patient experienced no significant episodes of bleeding even in operation and delivery, despite the severely decreased FXI activity at 1%. Patient has a prolonged aPTT: 69.3 s.	Kwon et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1556G>A

p.Trp519* (Legacy AA No. 501)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Nonsense

No. of Patients Reported:

14

Phenotype:

I

Allele Count *:

8

Allele Number *:

251434

Allele Frequency *:

0.000032

Variant Comments & Reference:

Disrupts catalytic domain structure. Saunders et al 2005, Colakoglu et al 2018, Zhang et al 2020, Yang et al 2021

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
66	65	M	Japanese	<5	Undetectable	Homozygote		Severe	No apparent bleeding tendancy noted in past history, pa tient was admitted with non-specific multiple ulcers.	Iijima et al 2000
517	11	F	Turkish			Heterozygote		Not Reported	Bruising, bleeding from minor wounds, bleeding after tooth extraction, oral bleeding and gastrointestinal bleeding	Colakoglu et al 2018
521	45	F	Turkish			Heterozygote		Not Reported	Asymptomatic	Colakoglu et al 2018
547	12	F	Italian	6		Compound heterozygote	c.901T>C (p.Phe301Leu)	Not Reported	Surgery-related bleeding	Tiscia et al 2017
548	45	M	Italian	114		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
550	7	M	Italian	47		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
551	31	F	Italian	7		Compound heterozygote	c.943G>A (p.Glu315Lys)	Not Reported	Vaginal bleeding during pregnancy	Tiscia et al 2017
552	54	M	Italian	36		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
674		F				Compound heterozygote	c.1103G>A (p.Gly368Glu)	Not Reported	Reduced FXI activity and antigen levels to 1% and 1.3% of normal, respectively.	Yang et al 2021
677		F				Heterozygote		Not Reported		Yang et al 2021
678		M				Heterozygote		Not Reported		Yang et al 2021
684	26	F		<1		Compound heterozygote	c.1021G>A (p.Glu341Lys)	Severe	Intra-articular bleeding	Zhang et al 2020
688	25	F		<1		Compound heterozygote	c.1575_1576delAG	Severe	Menorrhagia	Zhang et al 2020
690	52	M		1.7		Compound heterozygote	c.1136-4delGTTG	Severe	Post-traumatic hemorrhage	Zhang et al 2020

Structural Interpretation:

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

c.1556G>C

p.Trp519Ser (Legacy AA No. 501)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Variant likely deleterious. Shao et al 2016, Liu et al 2019

Patient Information: Show

Patient_ID	Gender	Inheritance	Other Variants	Severity	Comments	Reference
660	F	Compound heterozygote	c.738G>A (p.Trp246*)	Not Reported	Reduced FXI activity and antigen levels to 6% and 10.7% of normal, respectively.	Liu et al 2019
664	F	Heterozygote		Not Reported		Liu et al 2019
665	M	Heterozygote		Not Reported		Liu et al 2019
666	M	Heterozygote		Not Reported		Liu et al 2019

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1557G>C

p.Trp519Cys (Legacy AA No. 501)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

1

Allele Number *:

251432

Allele Frequency *:

0.000004

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
48	38	F	Lebanese	2	<1	Homozygote		Severe	Patient experienced few bleedings, except for two post-partum haemorrhages. No history of severe mucocutaneous bleeding or haemarthrosis.	de Moerloose et al 2004
49		F	Lebanese	36	36	Heterozygote		Mild		de Moerloose et al 2004
50		M	Lebanese	40	32	Heterozygote		Mild		de Moerloose et al 2004
509				2	<1	Compound heterozygote	c.1832T>G (p.Val611Gly)	Not Reported		Unpublished Data

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1562A>G

p.Tyr521Cys (Legacy AA No. 503)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

A>G

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Su et al 2018

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Severity	Reference
607	64	F	Chinese	13	76	Homozygote	Not Reported	Su et al 2018
608		F	Chinese	38	93	Heterozygote	Not Reported	Su et al 2018
609		F	Chinese	42	102	Heterozygote	Not Reported	Su et al 2018
610		M	Chinese	37	98	Heterozygote	Not Reported	Su et al 2018

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1608G>C

p.Lys536Asn (Legacy AA No. 518)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

1

Allele Number *:

251446

Allele Frequency *:

0.000004

Variant Comments & Reference:

The novel missense mutation FXI Lys536Asn leads to the replacement of the Lys536 which is part of a LxxxxxPxxxxxxC motif (x-variable amino acid) that occurs in several subfamilies of serine proteases. Although this motif is highly conserved between FXI and pre-kallikrein (86% sequence identity), the Lys536 is not conserved. On the other hand, this residue is conserved in human, murine and bovine FXI indicating that this is a FXI-specific amino acid. A molecular model of FXI predicts that the side-chain of this residue is on the surface of the molecule, possibly H-bonded to W515. Replacement of the positively charged lysine side chain by the smaller, neutral side chain of asparagine may interfere with the folding of the FXI molecule and/or secretion, leading to low antigen level. Alternatively, the secreted FXI variant may have a shortened plasma half-life. Ventura et al 2000, Esteban et al 2017

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.1026G>T (p.Gly342=)	Severe	Excessive bleeding after dental extraction. Menorrhagia.	Ventura et al 2000
55		F	Portuguese	1	12	Compound heterozygote	c.1026G>T (p.Gly342=)	Severe	Non-bleeder.	Ventura et al 2000
95		M	Portuguese			Heterozygote		Mild		Ventura et al 2000
601	47	F	Spanish	3		Compound heterozygote	c.1796G>A (p.Cys599Tyr)	Not Reported		Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1613C>T

p.Pro538Leu (Legacy AA No. 520)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

9

Phenotype:

II

Allele Count *:

27

Allele Number *:

282666

Allele Frequency *:

0.000096

Variant Comments & Reference:

Mutant protein is expressed in 293 human kidney fibroblasts. Activated mutant has a modest catalytic defect in functional assays. The basis of catalytic defect that results from Pro538Leu alteration is due to subtle alterations in the oxyanion hole, which develops during conversion of zymogen to active enzyme, and results in a ~3.5-fold decrease in catalytic efficiency, consistent with the 70-80% loss of activity noted in conventional coagulation assays. Thus, Pro538 is important in maintaining the normal conformation of the FXI active site. Pro538 is conserved in FX and FVII, and its mutation in both these other proteins also causes Type II phenotypes.This variant was not activated by FXIIa. Gailani et al 2001 (Abstract), Gailani et al 2007, Saunders et al 2009, Esteban et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
83	8on	M		34		Heterozygote		Not Reported	Prolonged bleeding from a scratch on the nose that required cautery.	Gailani et al 2001 Abstract B
179	65	F		43	90	Heterozygote		Not Reported	Patient also has von Willebrand disease	Hill et al 2005
180	47	F		48		Heterozygote		Not Reported	Easy bruising, menorrhagia	Hill et al 2005
205		M	French	30		Compound heterozygote	c.783G>C (p.Glu261Asp)	Not Reported		Quelin et al 2005
256			UK Population	48	80	Heterozygote		Not Reported		Mitchell et al 2006
257			UK Population	53		Heterozygote		Not Reported		Mitchell et al 2006
494		F		50	74	Heterozygote		Not Reported	No bleeding Hx.	Quelin et al 2009
599	71	M	Spanish	20		Homozygote		Not Reported		Esteban et al 2017
600	88	F	Spanish	59		Heterozygote		Not Reported		Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1619T>G

p.Val540Gly (Legacy AA No. 522)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

T>G

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Affect the catalytic activity of activated FXI. Colakoglu et al 2018

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
515	26	F	Turkish			Heterozygote		Not Reported	Asymptomatic	Colakoglu et al 2018

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1634G>A

p.Cys545Tyr (Legacy AA No. 527)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

1

Allele Number *:

251462

Allele Frequency *:

0.000004

Variant Comments & Reference:

Expression of Cys545Tyr in BHK cells revealed intact dimerisation, a reduced amount of FXI in lysed cells and total lack of secretion from the cells. Zucker et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
495	24	F	Belgic	<2	<5	Compound heterozygote	c.943G>A (p.Glu315Lys)	Severe	Bleeding after tooth extraction.	Zucker et al 2007

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1682G>A

p.Ala561Asp (Legacy AA No. 543)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Damaging effect on FXI structure. Tiscia et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
561	3	F	Italian	34		Compound heterozygote	c.943G>A (p.Glu315Lys)	Not Reported	Asymptomatic	Tiscia et al 2017
562	30	F	Italian	36		Compound heterozygote	c.943G>A (p.Glu315Lys)	Not Reported	Asymptomatic	Tiscia et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1684G>A

p.Gly562Ser (Legacy AA No. 544)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

10

Allele Number *:

251490

Allele Frequency *:

0.000040

Variant Comments & Reference:

Gly562Ser resides on a surface exposed loop within the SP domain and it is not clear whether this is the causative mutation because the patients mother has the mutation but has normal FXI:C levels. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
496				62		Heterozygote		Not Reported		Saunders et al 2009
497				105		Heterozygote		Not Reported	Mother of patient 496	Saunders et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1693G>A

p.Glu565Lys (Legacy AA No. 547)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

10

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Responsible for an aberrant splicing in which exon 13 is skipped. Saunders et al 2009, Esteban et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
177	54	F		49	37	Heterozygote		Mild	Post Partum Haemorrhage	Hill et al 2005
178	32	F		25	18	Heterozygote		Mild	2 Post-partum haemorrhage, no spontaneous bleeding	Hill et al 2005
203	33	F	French	23	32	Heterozygote		Not Reported	Epistaxis	Quelin et al 2005
465	9	F	Iranian	35		Compound heterozygote	c.1169G>C (p.Gly390Ala)	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
593	26	F	Spanish	30		Heterozygote		Not Reported		Esteban et al 2017
594	44	F	Spanish	41		Heterozygote		Not Reported		Esteban et al 2017
595	49	F	Spanish	36		Heterozygote		Not Reported		Esteban et al 2017
596	32	M	Spanish	45		Heterozygote		Not Reported		Esteban et al 2017
597	55	F	Spanish	32		Heterozygote		Not Reported		Esteban et al 2017
598	72	F	Spanish	63		Heterozygote		Not Reported		Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.1707C>T

p.Asp569= (Legacy AA No. 551)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Silent

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

4190

Allele Number *:

282698

Allele Frequency *:

0.014821

Variant Comments & Reference:

Polymorphism. Cargill et al 1999

Patient Information: Show

Structural Interpretation:

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

c.1717-2A>G

(Legacy AA No. 555)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

A>G

Variant Effect:

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

This point mutation interferes with normal splicing and results in a truncated protein. Fard-Esfahani et al 2008

Patient Information: Show

Structural Interpretation:

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

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