Factor XI Variant Database

c.1028+5G>T

-

Variant Type:

Point

Domain:

Apple 4

Codon Change:

G>T

Variant Effect:

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

1

Allele Number *:

251452

Allele Frequency *:

0.000004

Variant Comments & Reference:

This FXI mutation abolishes the splice site at the 3' boundary of exon 9. Saunders et al 2009

Patient Information: Show

Structural Interpretation:

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

c.1029-2A>G

-

Variant Type:

Point

Domain:

Apple 4

Codon Change:

A>G

Variant Effect:

No. of Patients Reported:

0

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Pugh et al 1995

Patient Information: Show

Structural Interpretation:

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

c.1072delA

-

Variant Type:

Deletion

Domain:

Apple 4

Codon Change:

delA

Variant Effect:

Frameshift

No. of Patients Reported:

2

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	Other Variants	Severity	Comments	Reference
58			Portuguese	1	15	Homozygote		Severe	Non-bleeder.	Ventura et al 2000
471	58	F	Portgugese	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 (Deletion | Frameshift) variant.

c.1135+1G>A

-

Variant Type:

Point

Domain:

Intronic

Codon Change:

G>A

Variant Effect:

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

3

Allele Number *:

250710

Allele Frequency *:

0.000012

Variant Comments & Reference:

Mutation changes an invariant nucleotide of the splicing site recognition sequence, and likely results in aberrant splicing of FXI mRNA causing FXI deficiency. Okumura et al 2006

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
153				<1		Heterozygote		Severe	Bleeding at hemostatic challenge and/or mild bleeding tendency	Hayashi et al 1997 Abstract
463	29	F	Japanese	50		Heterozygote		Not Reported		Okumura et al 2006

Structural Interpretation:

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

c.1136-4delGTTG

-

Variant Type:

Deletion

Domain:

Intronic

Codon Change:

delGTTG

Variant Effect:

Frameshift

No. of Patients Reported:

8

Phenotype:

I

Allele Count *:

1

Allele Number *:

251472

Allele Frequency *:

0.000004

Variant Comments & Reference:

Xie 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
155		F	Chinese	<10	<50	Homozygote		Severe		Xie et al 2005
156		M	Chinese	<10	<50	Homozygote		Severe		Xie et al 2005
268		F	Chinese	<10	<50	Homozygote		Severe		Xie et al 2005
620	6	F	Chinese	1		Compound heterozygote	c.1103G>A (p.Gly368Glu)	Not Reported	Epistaxis	Shao et al 2016
621	51	F	Chinese	5		Compound heterozygote	c.596-8T>A	Not Reported	Easy brusing, menorrhagia and bleeding upon tooth extraction	Shao et al 2016
622	12	F	Chinese	3		Compound heterozygote		Not Reported	Bleeding following injury/surgery - also carries L465CfsX1 mutation	Shao et al 2016
686	31	F		<1		Homozygote		Severe	Asymptomatic	Zhang et al 2020
690	52	M		1.7		Compound heterozygote	c.1556G>A (p.Trp519*)	Severe	Post-traumatic hemorrhage	Zhang et al 2020

Structural Interpretation:

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

c.1304+12G>A

-

Variant Type:

Point

Domain:

Intronic

Codon Change:

G>A

Variant Effect:

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

876

Allele Number *:

277074

Allele Frequency *:

0.003162

Variant Comments & Reference:

Intron 11. Saunders et al 2009

Patient Information: Show

Structural Interpretation:

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

c.1305-10T>A

-

Variant Type:

Point

Domain:

Intronic

Codon Change:

T>A

Variant Effect:

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

This mutation, in the polypyrimidine track of the intron K acceptor splice site affects FXI pre-mRNA splicing. It abolishes an AluI restriction site. This creates an alternative splice sites that results in the inclusion of intronic, or deletion of exonic nucleotides leading to frameshift. Ventura et al 2000

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
59			Portuguese	1		Homozygote		Severe	Excessive bleeding after dental extraction.	Ventura et al 2000

Structural Interpretation:

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

c.1322delT

-

Variant Type:

Deletion

Domain:

Serine Protease

Codon Change:

delT

Variant Effect:

Frameshift

No. of Patients Reported:

2

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
647	54	F	Taiwanese	1	4.1	Compound heterozygote	c.1107C>T (p.Tyr369=)	Not Reported	Easy bruising, menorrhagia and postpartum hemorrhage (Grade II bleeding)	Lin et al 2020
654	52	M	Taiwanese	<1		Homozygote		Not Reported	Asymptomatic	Lin et al 2020

Structural Interpretation:

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

c.1325delT

p.Leu442Cys-

Variant Type:

Deletion

Domain:

Serine Protease

Codon Change:

delT

Variant Effect:

Frameshift

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

14

Allele Number *:

282776

Allele Frequency *:

0.000050

Variant Comments & Reference:

Induces formation of premature termination codon. Shao et al 2016

Patient Information: Show

Structural Interpretation:

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

c.1448delT

-

Variant Type:

Deletion

Domain:

Serine Protease

Codon Change:

delT

Variant Effect:

Frameshift

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Induces formation of premature termination codon. Shao et al 2016

Patient Information: Show

Structural Interpretation:

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

c.1480+3A>T

-

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

A>T

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:

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

c.1481-215C>T

-

Variant Type:

Point

Domain:

Intronic

Codon Change:

C>T

Variant Effect:

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Polymorphism. Wiewel-Verschueren et al 2017

Patient Information: Show

Structural Interpretation:

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

c.1481-34G>T

-

Variant Type:

Point

Domain:

Intronic

Codon Change:

G>T

Variant Effect:

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

17359

Allele Number *:

282360

Allele Frequency *:

0.061478

Variant Comments & Reference:

Polymorphism. Wiewel-Verschueren et al 2017

Patient Information: Show

Structural Interpretation:

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

c.1481-188C>T

-

Variant Type:

Point

Domain:

Intronic

Codon Change:

C>T

Variant Effect:

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Polymorphism. Wiewel-Verschueren et al 2017

Patient Information: Show

Structural Interpretation:

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

c.1556insG

-

Variant Type:

Insertion

Domain:

Serine Protease

Codon Change:

insG

Variant Effect:

Frameshift

No. of Patients Reported:

7

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	Other Variants	Severity	Comments	Reference
47			Japanese			Compound heterozygote	c.716T>C (p.Phe239Ser)	Severe		Morishita et al 2003 (Abstract)
69	25	M	Japanese	Undetectable	Undetectable	Compound heterozygote	c.1393G>T (p.Glu465*)	Severe	Asymptomatic - no abnormal bleeding history.	Tsukahara et al 2003
303		F	Iranian	35		Heterozygote		Not Reported	Prolonged PTT	Fard-Esfahani et al 2008
424			Japanese			Compound heterozygote	c.716T>C (p.Phe239Ser)	Not Reported		Kuroda et al 2005 (Abstract)
484	2	M	Japanese	<1		Compound heterozygote	c.1394C>G (p.Gln451Glu)	Severe	No history of episodes of excessive bleeding.	Ishikawa et al 2007
485	4	M	Japanese	4		Compound heterozygote	c.1394C>G (p.Gln451Glu)	Not Reported	Frequent epistaxis.	Ishikawa et al 2007
488		F	Japanese	54		Heterozygote		Not Reported	Patient's husband is heterozygous for Gln433Glu mutation. They have three children, two of which are compound heterozygous for Gln433Glu and c.1556dupG whilst the third child is heterozygous Gln433Glu	Ishikawa et al 2007

Structural Interpretation:

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

c.1560dupG

-

Variant Type:

Duplication

Domain:

Serine Protease

Codon Change:

dupG

Variant Effect:

Frameshift

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Mutation inserts an additional G in a stretch of five guanine nucleotides at nucleotide position 1560. This leads to a frameshift, generating a premature termination codon at position 535 [Tyr503ValfsX32]. 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.1546G>A (p.Val516Met)	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:

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

c.1574-93dupAT

-

Variant Type:

Duplication

Domain:

Intronic

Codon Change:

dupAT

Variant Effect:

Frameshift

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Polymorphism. Peretz et al 1997

Patient Information: Show

Structural Interpretation:

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

c.1575_1576delAG

-

Variant Type:

Deletion

Domain:

Serine Protease

Codon Change:

delAG

Variant Effect:

Frameshift

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Zhang et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
688	25	F		<1		Compound heterozygote	c.1556G>A (p.Trp519*)	Severe	Menorrhagia	Zhang et al 2020

Structural Interpretation:

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

c.1576+51C>A

-

Variant Type:

Point

Domain:

Intronic

Codon Change:

G>T

Variant Effect:

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

17287

Allele Number *:

281500

Allele Frequency *:

0.061410

Variant Comments & Reference:

Polymorphism. Wiewel-Verschueren et al 2017

Patient Information: Show

Structural Interpretation:

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

c.1714_1716+11del

-

Variant Type:

Deletion

Domain:

Serine Protease

Codon Change:

Variant Effect:

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Jewish Type IV. Peretz et al 1996

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
68	30	M	Jewish	<1	<10	Compound heterozygote	c.403G>T (p.Glu135*)	Severe		Peretz et al 1996

Structural Interpretation:

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

c.1716+1G>A

-

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Jewish Type I mutation. Saunders et al 2005, Peretz et al 2013

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
78	44	M	Ashkenazi Jewish	<10	<10	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	Mild - few episodes of mild but significant bleeding	Asakai et al 1989
260			UK Population	71		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

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

c.1716+248G>A

-

Variant Type:

Point

Domain:

Intronic

Codon Change:

G>A

Variant Effect:

No. of Patients Reported:

2

Phenotype:

None

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Polymorphism. Wiewel-Verschueren et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
555	7	F	Italian	37		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
556	48	F	Italian	60		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017

Structural Interpretation:

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

c.1717-1G>A

-

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Zhang et al 2020

Patient Information: Show

Structural Interpretation:

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

c.1717-48A>G

-

Variant Type:

Point

Domain:

Intronic

Codon Change:

A>G

Variant Effect:

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

17467

Allele Number *:

281898

Allele Frequency *:

0.061962

Variant Comments & Reference:

Polymorphism. Cargill et al 1999

Patient Information: Show

Structural Interpretation:

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

c.3G>T

p.Met1Ile (Legacy AA No. -18)

Variant Type:

Point

Domain:

Signal Peptide

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

I

Allele Count *:

1

Allele Number *:

31402

Allele Frequency *:

0.000032

Variant Comments & Reference:

Mutations affecting the ATG initiation codon have not been widely reported, and the loss of the initiation methionine in the Met1Ile variant was expected to be severely detrimental to protein synthesis and secretion. Expression studies show that no FXI is secreted, but surprisingly apparently normal (160 kDa) dimeric FXI was detected by western blot from cell lysates. Mitchell et al 2007

Patient Information: Show

Patient_ID	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Reference
214	UK Population	<1	<3	Compound heterozygote	c.438C>A (p.Cys146*)	Severe	Mitchell et al 2006
215	UK population			Heterozygote		Not Reported	Mitchell et al 2006
373		43		Heterozygote		Not Reported	Mitchell et al 2007

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.15T>A

p.Tyr5* (Legacy AA No. -14)

Variant Type:

Point

Domain:

Signal Peptide

Codon Change:

T>A

Variant Effect:

Nonsense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Neerman-Arbez et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
400				0.02		Compound heterozygote	c.403G>T (p.Glu135*)	Severe		Neerman-Arbez et al 2007

Structural Interpretation:

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

c.44C>T

p.Ser15Leu (Legacy AA No. -4)

Variant Type:

Point

Domain:

Signal Peptide

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Quelin et al 2006

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
190	36	F	Morrocan	3	3	Homozygote		Not Reported		Quelin et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.52G>C

p.Gly18Arg (Legacy AA No. -1)

Variant Type:

Point

Domain:

Signal Peptide

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Signal peptide prediction analysis results showed that this mutation would disrupt the original signal peptide cutting site between -1 and +1 amino acid position, resulting in impaired secretion of the synthesised FXI protein. Wang et al 2009

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.55G>A

(Legacy AA No. 1)

Variant Type:

Point

Domain:

Linker

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Zhang et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
682	39	M		6.4		Compound heterozygote	c.1021G>A (p.Glu341Lys)	Severe	Asymptomatic	Zhang et al 2020

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.55G>T

p.Glu19* (Legacy AA No. 1)

Variant Type:

Point

Domain:

Linker

Codon Change:

G>T

Variant Effect:

Nonsense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Mitchell et al 2006

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
213			Uk Population	43		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

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

c.67C>T

p.Gln23* (Legacy AA No. 5)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

3

Allele Number *:

251420

Allele Frequency *:

0.000012

Variant Comments & Reference:

Castaman et al 2007 (ISTH Abstract)

Patient Information: Show

Structural Interpretation:

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

c.100G>C

p.Asp34His (Legacy AA No. 16)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

I

Allele Count *:

2

Allele Number *:

251446

Allele Frequency *:

0.000008

Variant Comments & Reference:

Amount of mutant protein secreted from cells in vitro is reduced. The replacement of Asp 34 in the Ap1 domain of factor XI is a radical substitution, because the wild-type Asp side chain is small and negatively charged at physiologic pH, whereas the His group is bulky and hydrophobic with neutral charge - the alteration of charge and shape and the resultant conformational change of this region of the molecule might interfere with chain folding. Pugh et al 1995

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.113T>C

p.Val38Ala (Legacy AA No. 20)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Substitution of FXI-Val38 by Ala in BHK cells caused profoundly decreased FXI secretion (22% of wild-type by cells) despite the presence of only slightly reduced amounts of FXI dimer within the cells. Zivelin et al 1999 (Abstract 2), Zucker et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
280	34	F	French		32	Heterozygote		Not Reported	Asymptomatic	Zucker et al 2007

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.122C>T

p.Pro41Leu (Legacy AA No. 23)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Quelin et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
199	34	F	French	30	39	Heterozygote		Not Reported		Quelin et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.122C>A

p.Pro41Gln (Legacy AA No. 23)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Mitchell et al 2006

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
216			UK Population	56		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.126C>G

p.Ser42Arg (Legacy AA No. 24)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>G

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Ser42Arg lies at the start of helix A1 within the Ap1 domain. In the crystal structure, this sidechain points towards the interdomain contacts with the Ap2 domain and the replacement with a larger charged residue is predicted to affect the protein structure. Saunders et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
402				29		Heterozygote		Not Reported		Saunders et al 2009
616	44	F	Chinese	2		Compound heterozygote	c.326-1G>A	Not Reported	Bleeding following injury/surgery and menorrhagia	Shao et al 2016

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.127G>A

p.Ala43Thr (Legacy AA No. 25)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

9

Allele Number *:

251460

Allele Frequency *:

0.000036

Variant Comments & Reference:

Heterodimer trapping. Duga & Salomon 2013

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.137G>T

p.Cys46Phe (Legacy AA No. 28)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

3

Allele Number *:

251460

Allele Frequency *:

0.000012

Variant Comments & Reference:

This mutation represents a structurally significant change as it abolishes a Cys46-Cys76 disulphide bridge that is essential for the folding of the first apple domain. Zivelin et al 2002, Hill et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
165	15	F		24	35	Heterozygote		Mild	Menorrhagia	Hill et al 2005
166	10	F		31	41	Heterozygote		Mild	Easy bruising, epistaxis, bleeding gums	Hill et al 2005
167	45	M		26		Heterozygote		Mild	Bleeding postdental extraction	Hill et al 2005
617	32	F	Chinese	1		Compound heterozygote	c.738G>A (p.Trp246*)	Not Reported	Easy bruising and menorrhagia	Shao et al 2016

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.141G>C

p.Gln47His (Legacy AA No. 29)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

17

Allele Number *:

251470

Allele Frequency *:

0.000068

Variant Comments & Reference:

Mutant protein was not secreted by transfected HEK293 cells. Bolton-Maggs et al 2003 (Abstract)

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.151A>C

p.Thr51Pro (Legacy AA No. 33)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

A>C

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Thr51Pro and Thr51Ile. These changes convert hydrophilic and moderately sized threonine to hydrophobic, large proline and isoleucine, respectively. Thr51 lies in the first a-helix, in a buried region of Apple 1 domain and just next to a cysteine residue which forms the disulphide bond. On the other hand, the threonine residue is conserved in positions 51, 141, 231 and 322 of four Apple domains, in the same position relative to the a-helix of each domain. Therefore, it seems that this amino acid is essential for proper function of the protein and its alteration is not conservative. Fard-Esfahani et al 2008, Colakoglu et al 2018

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
518	7	M	Turkish			Heterozygote		Not Reported	Epistaxis	Colakoglu et al 2018
524	10	F	Turkish			Heterozygote		Not Reported	Epistaxis	Colakoglu et al 2018

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.152C>T

p.Thr51Ile (Legacy AA No. 33)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Thr51Pro and Thr51Ile. These changes convert hydrophilic and moderately sized threonine to hydrophobic, large proline and isoleucine, respectively. Thr51 lies in the first a-helix, in a buried region of Apple 1 domain and just next to a cysteine residue which forms the disulphide bond. On the other hand, the threonine residue is conserved in positions 51, 141, 231 and 322 of four Apple domains, in the same position relative to the a-helix of each domain. Therefore, it seems that this amino acid is essential for proper function of the protein and its alteration is not conservative. Fard-Esfahani et al 2008

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.166T>C

p.Cys56Arg (Legacy AA No. 38)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

36

Phenotype:

I

Allele Count *:

3

Allele Number *:

251464

Allele Frequency *:

0.000012

Variant Comments & Reference:

High prevalence in French Basque population. Mutant protein synthesized in BHK transfected cells but not secreted. Zivelin et al 2002, Esteban et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
1	50	F	French Basque	<1		Homozygote		Severe	No bleeding after breast surgery	Zivelin et al 2002
2	22	F	French Basque	2		Compound heterozygote	c.1531T>C (p.Tyr511His)	Severe	No bleeding after an open fracture	Zivelin et al 2002
3	35	F	French Basque	30		Heterozygote		Mild		Zivelin et al 2002
6	40	M	French Basque	36		Heterozygote		Mild	Hematoma following cervical disc surgery	Zivelin et al 2002
7	34	F	French Basque	18		Heterozygote		Mild	Mild bleeding after delivery	Zivelin et al 2002
97	22	F	French Basque	1		Compound heterozygote	c.1531T>C (p.Tyr511His)	Severe	No bleeding after dental extraction	Zivelin et al 2002
98	22	M	French Basque	40		Heterozygote		Mild	No bleeding after herniorrhaphy	Zivelin et al 2002
99	28	M		40		Heterozygote		Mild		Zivelin et al 2002
100	53	F		45		Heterozygote		Mild		Zivelin et al 2002
101	61	M	French Basque	34		Heterozygote		Mild		Zivelin et al 2002
102	51	F	French Basque	40		Heterozygote		Mild		Zivelin et al 2002
209	58	M	French	<1	<1	Compound heterozygote	c.1199C>T (p.Pro400Leu)	Severe		Quelin et al 2005
563	52	M	Spanish	1		Homozygote		Not Reported		Esteban et al 2017
564	45	F	Spanish	3		Homozygote		Not Reported		Esteban et al 2017
565	53	F	Spanish	41		Heterozygote		Not Reported		Esteban et al 2017
566	41	M	Spanish	36		Heterozygote		Not Reported		Esteban et al 2017
567	52	M	Spanish	30		Heterozygote		Not Reported		Esteban et al 2017
568	47	M	Spanish	38		Heterozygote		Not Reported		Esteban et al 2017
569	43	M	Spanish	41		Heterozygote		Not Reported		Esteban et al 2017
570	63	F	Spanish	42		Heterozygote		Not Reported		Esteban et al 2017
571	51	M	Spanish	40		Heterozygote		Not Reported		Esteban et al 2017
572	40	F	Spanish	44		Heterozygote		Not Reported		Esteban et al 2017
573	57	M	Spanish	44		Heterozygote		Not Reported		Esteban et al 2017
574	53	F	Spanish	41		Heterozygote		Not Reported		Esteban et al 2017
575	44	F	Spanish	37		Heterozygote		Not Reported		Esteban et al 2017
576	47	M	Spanish	37		Heterozygote		Not Reported		Esteban et al 2017
577	32	F	Spanish	34		Heterozygote		Not Reported		Esteban et al 2017
578	79	M	Spanish	28		Heterozygote		Not Reported		Esteban et al 2017
579	58	F	Spanish	42		Heterozygote		Not Reported		Esteban et al 2017
580	42	M	Spanish	49		Heterozygote		Not Reported		Esteban et al 2017
581	68	M	Spanish	40		Heterozygote		Not Reported		Esteban et al 2017
582	49	M	Spanish	68		Heterozygote		Not Reported		Esteban et al 2017
583	52	M	Spanish	58		Heterozygote		Not Reported		Esteban et al 2017
584	59	F	Spanish	42		Heterozygote		Not Reported		Esteban et al 2017
585	49	M	Spanish	25		Heterozygote		Not Reported		Esteban et al 2017
586	71	F	Spanish	2		Compound heterozygote	c.1247G>A (p.Cys416Tyr)	Not Reported		Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.168T>A

p.Cys56* (Legacy AA No. 38)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

T>A

Variant Effect:

Nonsense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Ramadan et al 2006

Patient Information: Show

Structural Interpretation:

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

c.168T>G

p.Cys56Trp (Legacy AA No. 38)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

T>G

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Cys56 is a buried residue located in a random coil of Ap1 and is involved in the Cys50-Cys56 disulphide bridge. This disulphide bridge represents one of three conserved bridges that are responsible for the correct folding of the Ap domains. Therefore, Cys56Trp mutation is likely to significantly impair folding of the Ap1 domain. Expression studies reveal a secretion defect. Castaman et al 2005, Spena et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
511			Italian	20	46	Heterozygote		Not Reported	FXI:C/FXI:Ag ratio = 0.435. Asymptomatic.	Spena et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.197C>T

p.Pro66Leu (Legacy AA No. 48)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

18

Allele Number *:

282848

Allele Frequency *:

0.000064

Variant Comments & Reference:

Polymorphism. Cargill et al 1999

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.209C>T

p.Pro70Leu (Legacy AA No. 52)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

1

Allele Number *:

251440

Allele Frequency *:

0.000004

Variant Comments & Reference:

Unpublished Data From Coagulation factor XI: a database of mutations and polymorphism associated with factor XI deficiency http://www.wienkav.at/kav/factorxi/Faktor_XI_Suche.asp

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.214C>T

p.Arg72* (Legacy AA No. 54)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

1

Allele Number *:

251432

Allele Frequency *:

0.000004

Variant Comments & Reference:

Castaman et al 2005

Patient Information: Show

Structural Interpretation:

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

c.215G>C

p.Arg72Pro (Legacy AA No. 54)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Arg72 is part of an elaborated turning loop connecting the fourth and fifth strands. Electrostatic interactions among Arg72, Glu68 and Asp69 help to maintain the loop architecture. The Arg72Pro mutation eliminates these interactions and results in three close Pro residues, making the loop quite rigid and altering its structure and electrostatic surface. Spena et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
512		F	Czech	63	77	Heterozygote		Not Reported	FXI:C/FXI:Ag ratio = 0.81. Patient is asymptomatic: four dental extractions, tonsillectomy and one delivery without prophylaxis.	Spena et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.224C>T

p.Thr75Ile (Legacy AA No. 57)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Quelin et al 2009

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.226G>C

p.Cys76Arg (Legacy AA No. 58)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Mitchell et al 2006

Patient Information: Show

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).

Variant Comments & Reference:

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Structural Interpretation:

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UNIQUE (Without Patient Data) :

EXCEL/CSV

TABULAR

MULTIPLE (With Patient Data) :

EXCEL/CSV

TABULAR