Factor XI Variant Database

c.227G>A

p.Cys76Tyr (Legacy AA No. 58)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Abrogation of FXI secretion. This mutation disrupts the Cys76-Cys46 bond that is one of the three disulphide bonds responsible for correct folding of the Ap1 domain. Expression studies revealed intact FXI dimerization but no secretion at all from BHK cells. Zucker et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
147			Jewish	26		Heterozygote		Not Reported	No bleeding tendency	Zivelin et al 1999 (Abstract)

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.227G>T

p.Cys76Phe (Legacy AA No. 58)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

G>T

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
219			UK Population	<1		Homozygote		Severe		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.259C>A

p.Pro87Thr (Legacy AA No. 69)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>A

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
208	2	M	French	18	13	Compound heterozygote	c.1432G>A (p.Gly478Arg)	Not Reported		Quelin et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.290G>C

p.Gly97Ala (Legacy AA No. 79)

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:

Gly97Ala occurs in the C terminal portion of Ap1 domain, which contains the binding sites for HK, thrombin and prothrombin. Alanine at position 97 is predicted to introduce two novel hydrogen bonds with the nearby Phe59, probably affecting the local conformation of the protein. Gly97 is strictly conserved in four FXI apple domains of all species and also in kallikrein apple domains. Castaman et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
336			Czech	1	3	Compound heterozygote	c.403G>T (p.Glu135*)	Not Reported		Castaman et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.296C>A

p.Ser99Tyr (Legacy AA No. 81)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

C>A

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

1

Allele Number *:

251272

Allele Frequency *:

0.000004

Variant Comments & Reference:

Ser99Tyr is fully buried at the end of Î²-strand G in the Ap1 domain, thus the replacement with a bulky Tyr residue is expected to disrupt the protein folding. Saunders et al 2009

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.302A>G

p.Lys101Arg (Legacy AA No. 83)

Variant Type:

Point

Domain:

Apple 1

Codon Change:

A>G

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

3

Allele Number *:

251288

Allele Frequency *:

0.000012

Variant Comments & Reference:

Lys101 is a highly conserved residue positioned near Cys103, which is involved in a disulphide linkage. Although this substitution involves amino acids with similar physical and chemical properties, the change may affect local conformation. Hill et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
168	38	M		38		Heterozygote		Mild	Asymptomatic	Hill et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.316C>T

p.Gln106* (Legacy AA No. 88)

Variant Type:

Point

Domain:

Linker

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

5

Phenotype:

I

Allele Count *:

1

Allele Number *:

251302

Allele Frequency *:

0.000004

Variant Comments & Reference:

Quelin et al 2004

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
23	64	F	Nantes	60	51	Heterozygote		Mild	No excessive bleeding after appendicectomy, cholecysteco my or delivery.	Quelin et al 2004
24	41	M	Nantes	<1	0	Homozygote		Severe	No excessive bleeding after ligamentoplasty	Quelin et al 2004
25	36	F	Nantes	46	41	Heterozygote		Mild	No excessive bleeding after delivery x 3 or after appendicectomy	Quelin et al 2004
26	46	F	Nantes	<1	0	Homozygote		Severe	Patient treated with FXI concentrate before cholecystectomy and showed no excessive bleeding. Also given fresh frozen plasma before delive ry and showed no bleeding. Developed and inhibitor to FXI after exposure to FXI concentrate.	Quelin et al 2004
28	9	M	Nantes	<1	1	Compound heterozygote	c.192_193insG	Severe		Quelin et al 2004

Structural Interpretation:

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

c.325G>A

p.Ala109Thr (Legacy AA No. 91)

Variant Type:

Point

Domain:

Linker

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

11

Phenotype:

I

Allele Count *:

6

Allele Number *:

282654

Allele Frequency *:

0.000021

Variant Comments & Reference:

Being located at the last position of exon 4, within a native donor splice site, this mutation may affect the correct splicing of the F11 mRNA. RT-PCR assays performed on total RNA demonstrated that Ala91Thr abolishes the native donor splice site causing the skipping of the affected exon, eventually resulting in a frameshift followed by a premature termination codon. This mutation is predicted to lead to the synthesis of truncated FXI proteins. Such proteins might be recognised as abnormal by cellular quality control systems, resulting in intracellular retention and protein degradation. Mitchell et al 2006, Guella et al 2008, Duncan et al 2008, Tiscia et al 2017, 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
220			UK Population	9		Compound heterozygote	c.1021G>A (p.Glu341Lys)	Not Reported		Mitchell et al 2006
221			UK Population	45		Heterozygote		Not Reported		Mitchell et al 2006
222			UK Population	2		Compound heterozygote	c.438C>A (p.Cys146*)	Not Reported		Mitchell et al 2006
284		F	Italian	26	39	Heterozygote		Not Reported	Haemorrhagic episodes	Guella et al 2008
404	42	M		2		Compound heterozygote	c.365G>A (p.Gly122Asp)	Not Reported	APTT: 106 s	Duncan et al 2008
522	4	M	Turkish			Heterozygote		Not Reported	Asymptomatic	Colakoglu et al 2018
523	42	M	Turkish			Heterozygote		Not Reported	Asymptomatic	Colakoglu et al 2018
528	12	F	Italian	<1		Compound heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
529	37	M	Italian	32		Heterozygote		Not Reported	Epistaxis	Tiscia et al 2017
530	31	F	Italian	35		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
604	60	M	Spanish	37		Heterozygote		Not Reported		Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.328T>G

p.Cys110Gly (Legacy AA No. 92)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

T>G

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

The Cys110Gly mutation results in the loss of the C110-C193 disulfide bond and likely impairs the structure of the Ap2 domain. Thus, this mutation could alter the assembly and secretion of the protein. Quelin et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
200	43	M	French	47	40	Heterozygote		Not Reported		Quelin et al 2005
201	14	M	French	21	44	Heterozygote		Not Reported	Epistaxis	Quelin et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.359T>C

p.Met120Thr (Legacy AA No. 102)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

2

Allele Number *:

251262

Allele Frequency *:

0.000008

Variant Comments & Reference:

Met120 is a buried residue and is conserved across six species and prekallikrein. Replacement of the hydrophobic non-polar Met with a hydrophilic polar Thr is likely to be structurally disruptive. Expression studies indicate it is not expressed and type I. This amino acid substitution does not prevent the formation of dimers, despite the established role of the Ap2 domain in dimer formation. Mitchell et al 2006, Mitchell et al 2007

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.365G>A

p.Gly122Asp (Legacy AA No. 104)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

7

Phenotype:

I

Allele Count *:

2

Allele Number *:

282668

Allele Frequency *:

0.000007

Variant Comments & Reference:

Mitchell et al 2003

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
8				35		Heterozygote		Mild		Mitchell et al 2003
12				42		Heterozygote		Not Reported	Suffered from epistaxis	Alhaq et al 2000
117				33		Heterozygote		Mild		Mitchell et al 2003
224			UK Population	58	61	Heterozygote		Not Reported		Mitchell et al 2006
225			UK Population	44		Heterozygote		Not Reported		Mitchell et al 2006
404	42	M		2		Compound heterozygote	c.325G>A (p.Ala109Thr)	Not Reported	APTT: 106 s	Duncan et al 2008
440				45		Heterozygote		Not Reported		Saunders et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.400C>T

p.Gln134* (Legacy AA No. 116)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

3

Phenotype:

I

Allele Count *:

8

Allele Number *:

282680

Allele Frequency *:

0.000028

Variant Comments & Reference:

Dossenbach-Glaninger & Hopmeier 2006, Castaman et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
149			Austrian	10				Not Reported	Bleeding at hemostatic challenge and/or mild bleeding tendency	Dossenbach-Glaninger et al 2002
186			Austrian	52	43	Heterozygote		Not Reported		Dossenbach-Glaninger & Hopmeier 2006
407	61	M	Italian	1	4	Compound heterozygote	c.422C>T (p.Thr141Met)	Severe	Bleeding after knee arthroscopy - minor bleeding not requiring substitutive treatment	Castaman et al 2008

Structural Interpretation:

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

c.403G>T

p.Glu135* (Legacy AA No. 117)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

G>T

Variant Effect:

Nonsense

No. of Patients Reported:

61

Phenotype:

I

Allele Count *:

244

Allele Number *:

282694

Allele Frequency *:

0.000863

Variant Comments & Reference:

The Type II mutation (Glu135*) is the most common mutation in Jewish FXI-deficient patients. Saunders et al 2005, Wiewel-Verschueren et al 2017, Tiscia 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
17	67	M	Jewish	<3	<5	Compound heterozygote	c.901T>C (p.Phe301Leu)	Severe	History of postoperative and posttraumatic bleeding requiring multiple transfusions of fresh frozen plasma.	Martincic et al 1998
51		M	Portuguese	1	7	Homozygote		Severe	Excessive bleeding after dental extraction. Required multiple transfusions of fresh frozen plasma.	Ventura et al 2000
52		M	Portuguese	1	14	Homozygote		Severe	Moderate Bleeding. Haematomas after dental extraction.	Ventura et al 2000
53		F	Portuguese	4		Homozygote		Severe	Non-bleeder.	Ventura et al 2000
67	22	F	Bedouin	0				Severe	Patient was admitted because of vaginal bleeding during the fourth month of her first pregnancy. There were no prior bleeding episodes. Bleeding stopped after fr esh frozen plasma transfusions.	Hatskelzon et al 1996
68	30	M	Jewish	<1	<10	Compound heterozygote	c.1714_1716+11del	Severe		Peretz et al 1996
76	36	M	Ashkenazi Jewish	<10	<10	Compound heterozygote	c.901T>C (p.Phe301Leu)	Severe	Trivial - few mild but insignificant bleeding episodes.	Asakai et al 1989
77	50	F	Ashkenazi Jewish	<10	<10	Compound heterozygote	c.901T>C (p.Phe301Leu)	Severe	None	Asakai et al 1989
78	44	M	Ashkenazi Jewish	<10	<10	Compound heterozygote	c.1716+1G>A	Severe	Mild - few episodes of mild but significant bleeding	Asakai et al 1989
80	48	F	Ashkenazi Jewish	<10	<10	Compound heterozygote	c.901T>C (p.Phe301Leu)	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.901T>C (p.Phe301Leu)	Severe	Moderate - recurrent episodes of moderately severe bleeding, sometimes requiring a blood transfusion.	Asakai et al 1989
92		F	Portuguese	1		Homozygote		Severe	Non-bleeder.	Ventura et al 2000
93		M	Portuguese	2		Homozygote		Severe	Non-bleeder.	Ventura et al 2000
94		F	Portuguese	47	88	Heterozygote		Mild		Ventura et al 2000
103	10	M		<1			c.764G>A (p.Cys255Tyr)	Severe	No bleeding after testicular surgery following plasma treatment	Zivelin et al 2002
105	48	F	Bedouin	42				Mild		Hatskelzon et al 1996
106	11	M	Bedouin	30				Mild		Hatskelzon et al 1996
107	9	M	Bedouin	1				Severe		Hatskelzon et al 1996
108	13	F	Bedouin	59				Mild		Hatskelzon et al 1996
109	16	F	Bedouin	22				Mild		Hatskelzon et al 1996
110	18	F	Bedouin	43				Mild		Hatskelzon et al 1996
148			Jewish	2		Compound heterozygote	c.1334A>G (p.Tyr445Cys)	Not Reported		Zivelin et al 1999 (Abstract)
158	56	F	Italian	<1	0			Mild	Patient had normal menses and no bleeding tendency until the age of 24 years when a bleeding episode occured after a dental extraction. This did not require any transfusions. At the age of 52 she underwent right knee arthroscopy under prophylactic treatment with fresh-frozen-virus inactivated plasma. Recently prohylactic treatment was not given for a further minor orthopedic procedure and no bleeding complications occurred.	Zadra et al 2004
159	61	M	Italian	<1	0			Severe	Frequently suffered severe epistaxis, resolved by fresh frozen plasma infusion. Excessive bleeding occurred after dental extractions as a consequence of surgery.	Zadra et al 2004
160	29	M	Italian	<1	1			Severe	Patient has a thalassemia trait. He has not shown any bleeding symptoms. Recently he successfully underwent varicecele repair under treatment with fresh-frozen v irus-inactivated plasma.	Zadra et al 2004
163	32	M	Italian	<1	5	Compound heterozygote		Severe	Ecchymoses, hematomas and post-traumatic bleeding tendency.	Zadra et al 2004
183	12	M	Italian	35	33	Heterozygote		Not Reported	Recurrent epistaxis	Solda et al 2005
184	34	M	Italian	32	39	Heterozygote		Not Reported	Recurrent epistaxis	Solda et al 2005
189	41	F	Jewish	18		Heterozygote		Not Reported	Bleeding after delivery.	Quelin et al 2006
235			UK Population	<1	<3	Compound heterozygote	c.751C>T (p.Gln251*)	Severe		Mitchell et al 2006
272			French Basque			Compound heterozygote		Not Reported		Zivelin et al 1999 (Abstract 2)
279	2	F	Non-Ashkenazi Jewish	<1	<1	Compound heterozygote		Severe	Gingival bleeding	Zucker et al 2007
335			Non-Jewish			Compound heterozygote		Not Reported		Castaman et al 2007 (ISTH Abstract)
336			Czech	1	3	Compound heterozygote	c.290G>C (p.Gly97Ala)	Not Reported		Castaman et al 2008
351	18	F	Jewish	0.02		Compound heterozygote		Severe	Gastroenteritis with intestinal bleeding	Neerman-Arbez M et al 2007
383		F		<1		Compound heterozygote		Severe	transfusion for bleeding complications and post-operative bruising following ovariectomy	Quelin et al 2009
384		F		<1		Compound heterozygote		Severe	Post-operative bleeding following choecystectomy requiring no therapeutic intervention. Ovarian bruising following delivery. Patient sufferes from spontaneous bruising and gingivorrhagia.	Quelin et al 2009
388		M		<1	<1	Compound heterozygote		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
398	32	M	Italian	<1	5	Compound heterozygote		Severe	Ecchymoses, hematomas and post-traumatic bleeding tendency.	Zadra et al 2004
400				0.02		Compound heterozygote	c.15T>A (p.Tyr5*)	Severe		Neerman-Arbez et al 2007
418	32	M	Italian	<1	5	Compound heterozygote	c.644_649delTCGACA (p.Ile215_Asp216del)	Severe	Ecchymoses, hematomas and post-traumatic bleeding tendency.	Zadra et al 2004
419		F	French	<1		Compound heterozygote	c.688T>A (p.Cys230Ser)	Severe	Transfusion for bleeding complications and post-operative bruising following ovariectomy	Quelin et al 2009
420		F		<1		Compound heterozygote	c.688T>A (p.Cys230Ser)	Severe	Patient sufferes from spontaneous bruising and gingivorrhagia.Post-operative bleeding following cholecystectomy requiring no therapeutic intervention. Ovarian bruising following obstetric delivery.	Quelin et al 2009
441				<1	<1	Homozygote		Severe		Saunders et al 2009
442				<1	4	Homozygote		Severe		Saunders et al 2009
443				<1		Homozygote		Severe		Saunders et al 2009
444				6		Compound heterozygote	c.901T>C (p.Phe301Leu)	Not Reported		Saunders et al 2009
445				44		heterozygote		Not Reported		Saunders et al 2009
446				62		Heterozygote		Not Reported		Saunders et al 2009
447					3	Compound heterozygote	c.901T>C (p.Phe301Leu)	Not Reported		Saunders et al 2009
457	61	M	Italian	<0.5	4	Compound heterozygote	c.981C>A (p.Cys327*)	Severe		Castaman et al 2008
461		M		<1	<1	Compound heterozygote	c.1102G>A (p.Gly368Arg)	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
466	24	M	Iranian	16		Homozygote		Not Reported	Bleeding after circumcision requiring FFP for Rx and prophylaxis. No parent consanguinity. FXI activity of parents: mother 41%, father 47%.	Karimi et al 2009
483	44	F	Ashkenazi Jewish	<1	<1	Compound heterozygote	c.1334A>G (p.Tyr445Cys)	Severe	Menorrhagia	Zucker et al 2007
526	6	M	Turkish			Heterozygote		Not Reported	Epistaxis	Colakoglu et al 2018
527	60	M	Turkish			Heterozygote		Not Reported	Asymptomatic	Colakoglu et al 2018
531	30	F	Italian	38		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
532	80	M	Italian	42		Heterozygote		Not Reported	Superficial vein thrombosis	Tiscia et al 2017
533	40	F	Italian	34		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
534	58	F	Italian	<1		Compound heterozygote	Unspecified (C136R) (p.Cys136Arg)	Not Reported	Asymptomatic	Tiscia et al 2017
634	54	M	Indian	<1		Homozygote		Not Reported	Bleeding during laryngectomy	Kawankar et al 2016

Structural Interpretation:

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

Unspecified (C136R)

p.Cys136Arg (Legacy AA No. 118)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Tiscia et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
534	58	F	Italian	<1		Compound heterozygote	c.403G>T (p.Glu135*)	Not Reported	Asymptomatic	Tiscia et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.408C>A

p.Cys136* (Legacy AA No. 118)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

C>A

Variant Effect:

Nonsense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

3

Allele Number *:

251304

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
151			European	<1		Compound heterozygote	c.1199C>T (p.Pro400Leu)	Severe		Bolton-Maggs et al 1999 Abstract
161	36	M	Italian	<1	0			Mild	At the age of 23 he was treated with fresh-frozen plasma infusions after cervical disc surgery; subsequently he was treated with an antifibrinolytic drug after a dental extraction. No bleeding problems occurred agter either procedure.	Zadra et al 2004
162	15	F	Italian	<1	0			Mild	Prolonged PTT found prior to tonsillectomy. During childhood and puberty she had recurrent episodes of epistaxis and suffered from diffue ecchymoses.	Zadra et al 2004
226			UK Population	<1		Compound heterozygote	c.1199C>T (p.Pro400Leu)	Severe		Mitchell et al 2006

Structural Interpretation:

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

c.419G>A

p.Cys140Tyr (Legacy AA No. 122)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

5

Phenotype:

I

Allele Count *:

2

Allele Number *:

251282

Allele Frequency *:

0.000008

Variant Comments & Reference:

Cys140 is buried in an alpha-helix of Ap2 and is part of the Cys140-Cys146 conserved disulphide bridge that is (along with two other conserved disulphide bridges) responsible for the correct folding of the Ap domains. Therefore, the Cys140Tyr mutation is likely to significantly impair the folding of the Ap2 domain. Expression studies reveal a secretion defect. Quelin et al 2006, Spena et al 2009

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Severity	Comments	Reference
191	68	M		25		Heterozygote	Not Reported	No bleeding or therapy required after tonsillectomy or colectomy.	Quelin et al 2006
192	42	M		24		Heterozygote	Not Reported	Bleeding after dental extraction. Bleeding after kneecap removal requiring FFP therapy	Quelin et al 2006
193	31	M		31		Heterozygote	Not Reported	Easy bruising	Quelin et al 2006
295			Non-Jewish			Compound heterozygote	Not Reported		Castaman et al 2007 (ISTH Abstract)
513		M	Italian	4	3	Homozygote	Not Reported	FXI:C/FXI:Ag ratio = 1.17. Patient is asymptomatic: four dental extractions, one with delayed post-extraction oozing, three surgical procedures without prophylaxis.	Spena et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.422C>T

p.Thr141Met (Legacy AA No. 123)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

11

Allele Number *:

282690

Allele Frequency *:

0.000039

Variant Comments & Reference:

The Thr141Met mutation results in the introduction of a hydrophobic sulfur atom (Met) and the loss of hydrophilic hydroxyl group (Thr). Castaman et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
289	61	M	Italian	1	4	Compound heterozygote		Severe	Bleeding after knee arthroscopy - minor bleeding not requiring substitutive treatment	Castaman et al 2008
407	61	M	Italian	1	4	Compound heterozygote	c.400C>T (p.Gln134*)	Severe	Bleeding after knee arthroscopy - minor bleeding not requiring substitutive treatment	Castaman et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.423G>A

p.Thr141= (Legacy AA No. 123)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

G>A

Variant Effect:

Silent

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

1

Allele Number *:

251274

Allele Frequency *:

0.000004

Variant Comments & Reference:

Polymorphism. Wiewel-Verschueren et al 2017

Patient Information: Show

Structural Interpretation:

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

c.428A>C

p.Asp143Ala (Legacy AA No. 125)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

A>C

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Jerčić et al 2020

Patient Information: Show

Patient_ID	Gender	Race	FXI:C%	Inheritance	Severity	Comments	Reference
637	F	Croatian	49	Heterozygote	Not Reported	Menorrhagia and easy bruising. Excessive bleeding after cesarean section and during thyroidectomy	Jerčić et al 2020
638	F	Croatian	47	Heterozygote	Not Reported	Menorrhagia	Jerčić et al 2020
639	M	Croatian		Heterozygote	Not Reported	Asymptomatic	Jerčić et al 2020

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.429C>T

p.Asp143= (Legacy AA No. 125)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

C>T

Variant Effect:

Silent

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

10089

Allele Number *:

282660

Allele Frequency *:

0.035693

Variant Comments & Reference:

Polymorphism. Ventura et al 2000

Patient Information: Show

Structural Interpretation:

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

c.434A>G

p.His145Arg (Legacy AA No. 127)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

A>G

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

U

Allele Count *:

39

Allele Number *:

282700

Allele Frequency *:

0.000138

Variant Comments & Reference:

The His145Arg mutation occurs adjacent to the Cys140-Cys146 disulphide pairing in Ap2, responsible for creating the substrate binding site in FXIa. Castaman et al 2007 (ISTH Poster Abstract), Castaman et al 2013, Peng et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
611	45	F	Indonesian	27	125	Heterozygote		Not Reported	Asymptomatic	Cataman et al 2013
612	14	M	Indonesian	52	118	Heterozygote		Not Reported	Asymptomatic	Cataman et al 2013
613	12	M	Indonesian	56	157	Heterozygote		Not Reported	Asymptomatic	Cataman et al 2013
655	13	M	Taiwanese	7		Compound heterozygote	c.841C>T (p.Gln281*)	Not Reported	Easy bruising (Grade II bleeding)	Lin et al 2020

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.438C>A

p.Cys146* (Legacy AA No. 128)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

C>A

Variant Effect:

Nonsense

No. of Patients Reported:

22

Phenotype:

I

Allele Count *:

10

Allele Number *:

282710

Allele Frequency *:

0.000035

Variant Comments & Reference:

Founder mutation found in English patients. Peretz et al 1997

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
39	50	M	Non-Jewish	49	41	Heterozygote		Mild	History of excessive bleeding. Bled for 6 hours after dental extractions at age 17.	Imanaka et al 1995
60			North European Caucasian	4		Compound heterozygote	c.809A>T (p.Lys270Ile)	Severe	No active bleeding problems following laporoscopic sterilization.	Dai et al 2004
70	59	F	English/Irish	<1		Homozygote		Severe	Fall resulting in nasal trauma and prolonged bleeding.	Zacharski & French 1978
71	86	M	English	<2		Compound heterozygote		Severe	Patient also has a 1bp insertion in exon 4 on the other allele but this is not reported in detail.	Bolton-Maggs et al 2004
72	35	M	Scottish	65	64	Heterozygote		Mild	Bleed after dental extraction, tonsilliectomy, sinus surgery and appendectom y.	Bolton-Maggs et al 2004
73	50	M	English	<1	<1	Compound heterozygote		Severe	Misdiagnosed as hemophilia A.	Bolton-Maggs et al 2004
74	18	M	Irish	34	27	Heterozygote		Mild	Bled after cardiac catheter and after aortic valve replacement.	Bolton-Maggs et al 2004
75	63	F		<1		Homozygote		Severe	Long APTT as incidental findingm but previous history of bleeding after dilatation and curettage requiring blood transfusion and return to theater. Tonsillectomy as a child without recorded problems.	Bolton-Maggs et al 2004
88	63	M		38		Heterozygote		Not Reported	Cerebal hemorrhage after fall, but no bleeding after tonsilectomy or dental extraction in his youth.	Bolton-Maggs et al 2004
89	32	F	Scottish/English	45		Heterozygote		Not Reported	Easy bruising in pregnancy, no bleeding after wisdom teeth extraction	Bolton-Maggs et al 2004
90	54	F	English	46		Heterozygote		Not Reported	Extensive bruising of face and neck after wisdom teeth extraction aged 21	Bolton-Maggs et al 2004
91	50	F	English	16		Heterozygote		Not Reported	Menorrhagia, bruising after hysterectomy	Bolton-Maggs et al 2004
169	29	F		29	29			Not Reported	Post-Partum Haemorrhage	Hill et al 2005
170	33	F		44	38			Not Reported	Asymtomatic	Hill et al 2005
171	55	F		41				Not Reported	Post Partum Haemorrhage, epistaxis, postoperative bleed requiring transfusion	Hill et al 2005
214			UK Population	<1	<3	Compound heterozygote	c.3G>T (p.Met1Ile)	Severe		Mitchell et al 2006
222			UK Population	2		Compound heterozygote	c.325G>A (p.Ala109Thr)	Not Reported		Mitchell et al 2006
227			UK Population	<1		Compound heterozygote	c.452A>G (p.Tyr151Cys)	Severe		Mitchell et al 2006
240			UK Population	4		Compound heterozygote	c.809A>T (p.Lys270Ile)	Not Reported		Mitchell et al 2006
374		F		<1		Compound heterozygote		Severe	Menorrhagia and 'excess bleeding/bruising tendency'	Mitchell et al 2007
448				61		Heterozygote		Not Reported		Saunders et al 2009
504	65	M	Australian	<2		Compound heterozygote	31.5KbDeletion	Severe	Patient has a bleeding Hx.	Duncan et al 2008

Structural Interpretation:

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

c.449C>T

p.Thr150Met (Legacy AA No. 132)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

6

Phenotype:

I

Allele Count *:

1

Allele Number *:

251286

Allele Frequency *:

0.000004

Variant Comments & Reference:

Mitchell et al 2006, Saunders et al 2009, Tiscia et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
408				2	2	Compound heterozygote	c.1432G>A (p.Gly478Arg)	Not Reported		Saunders et al 2009
409				23		Heterozygote		Not Reported		Mitchell et al 2006
535	27	M	Italian	34		Heterozygote		Not Reported	Epistaxis	Tiscia et al 2017
536	49	M	Italian	52		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
537	12	M	Italian	37		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017
538	43	M	Italian	43		Heterozygote		Not Reported	Asymptomatic	Tiscia et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.452A>C

p.Tyr151Ser (Legacy AA No. 133)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

A>C

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Transfection experiments with mutant protein confirmed it is expressed at lower levels comparable to normal FXI. Expression studies confirm type I phenotype (CRM-). Bolton-Maggs et al 2003 (Abstract), Mitchell et al 2006

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	Inheritance	Severity	Comments	Reference
43		F		38	Homozygote	Mild		Bolton-Maggs et al 2003 Abstract
172	28	F		38		Not Reported	Menorrhagia	Hill et al 2005
229			UK Population	50	Heterozygote	Not Reported		Mitchell et al 2006
410				36	Heterozygote	Not Reported	No relevant information	Mitchell et al 2007

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.452A>G

p.Tyr151Cys (Legacy AA No. 133)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

A>G

Variant Effect:

Missense

No. of Patients Reported:

2

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
227			UK Population	<1		Compound heterozygote	c.438C>A (p.Cys146*)	Severe		Mitchell et al 2006
228			UK Population	47		Heterozygote		Not Reported		Mitchell et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.454G>C

p.Ala152Pro (Legacy AA No. 134)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

1

Allele Number *:

251280

Allele Frequency *:

0.000004

Variant Comments & Reference:

Saunders et al 2009

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.484C>T

p.Arg162Cys (Legacy AA No. 144)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

10

Allele Number *:

251330

Allele Frequency *:

0.000040

Variant Comments & Reference:

Dossenbach-Glaninger & Hopmeier 2003, Tiscia et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
131			Austrian	35		Heterozygote		Not Reported	Patient attended hospital for other reasons than bleeding disorders.	Dossenbach-Glaninger and Hopmeier 2

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.518G>A

p.Gly173Glu (Legacy AA No. 155)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

II

Allele Count *:

1

Allele Number *:

250424

Allele Frequency *:

0.000004

Variant Comments & Reference:

Functional effect; disturbs proposed FXIa binding loop. Alhaq et al 2000, Mitchell et al 2003, O''Connell et al 2005, Saunders et al 2009

Patient Information: Show

Patient_ID	FXI:C%	FXI:Ag(%)	Inheritance	Severity	Reference
450	43	64	Heterozygote	Not Reported	O'Connell et al 2005
451	41		Heterozygote	Not Reported	Alhaq et al 2000
452	30		Heterozygote	Not Reported	Saunders et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.569T>C

p.Leu190Pro (Legacy AA No. 172)

Variant Type:

Point

Domain:

Apple 2

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

3

Allele Number *:

249014

Allele Frequency *:

0.000012

Variant Comments & Reference:

Wu et al 2004 (Abstract)

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.596C>T

p.Ala199Val (Legacy AA No. 181)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Ala199 is located next to the conserved Cys200 residue that forms a disulphide bridge with Cys283 connecting the two ends of the Ap3 domain. The Ala199Val substitution interferes with the disulphide bond leading to a misfolded protein. de Raucourt et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
476	23	F	French	0.07	0.07	Compound heterozygote	c.1288G>A (p.Ala430Thr)	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

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.599G>A

p.Cys200Tyr (Legacy AA No. 182)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

10

Allele Number *:

251312

Allele Frequency *:

0.000040

Variant Comments & Reference:

Bolton-Maggs et al 2003 (Abstract), Duncan et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
233			UK Population	34		Heterozygote		Not Reported		Mitchell et al 2006
415	29	F		47		Heterozygote		Not Reported	Patient has bleeding Hx. Median aPTT time: 35 s.	Duncan et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.599G>C

p.Cys200Ser (Legacy AA No. 182)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Shao et al 2016, Lin et al 2020

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
648	60	F	Taiwanese	34		Heterozygote		Not Reported		Lin et al 2020
681	4	F		<1		Compound heterozygote	c.1253G>T (p.Gly418Val)	Severe	Epistaxis	Zhang et al 2020

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.604A>G

p.Arg202Gly (Legacy AA No. 184)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

A>G

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

II

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Transfection experiments of Arg202Gly-FXI show a 70% reduction in FXI activity, suggesting the Arg202Gly mutation might represent a CRM+ defect. Guella et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
416			Italian	69	121	Heterozygote		Not Reported	Asymptomatic	Guella et al 2008
417	24	F	Italian	46	10	Compound heterozygote	c.595+3A>G	Not Reported	No Hx of bleeding episodes.	Guella et al 2008

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.616T>C

p.Pro206Ser (Legacy AA No. 188)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

2

Allele Number *:

251354

Allele Frequency *:

0.000008

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
196	36	M	French	30		Heterozygote		Not Reported		Quelin et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.646G>A

p.Asp216Asn (Legacy AA No. 198)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

0

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.682C>T

p.Arg228* (Legacy AA No. 210)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

4

Allele Number *:

251444

Allele Frequency *:

0.000016

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
29	28	M	Lebanese	<1	3	Compound heterozygote	c.1060G>A (p.Gly354Arg)	Severe	No excessive bleeding after dental extractions and u pper limb fracture.	Quelin et al 2004
680	32	F		16		Heterozygote		Not Reported	Asymptomatic	Zhang et al 2020

Structural Interpretation:

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

c.688T>A

p.Cys230Ser (Legacy AA No. 212)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

T>A

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Cys230Ser in exon 7 suppresses a disulphide bond that maintains the 220-226 loop in the tertiary structure of the third apple domain. It is also possible that free cysteine affects other disulphide bonds such as the 226-255 bond. Aberrant or absent disulphide bonds may disrupt the protein structure leading to impaired secretion or function or increased clearance of misfolded proteins. Another mutation involving Cys230 has been described (Cys230Arg). The Cys230 residue is buried. As a consequence, the size or charge of the substituting Arg residue may contribute to protein structure disruption. In Cys230Ser however, neither size nor charge can account for the structure disruption, rather the suppression of disulphide bridges is likely to be the determinant of altered secretion. Quelin et al 2009

Patient Information: Show

Patient_ID	Gender	Race	FXI:C%	Inheritance	Other Variants	Severity	Comments	Reference
419	F	French	<1	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	Transfusion for bleeding complications and post-operative bruising following ovariectomy	Quelin et al 2009
420	F		<1	Compound heterozygote	c.403G>T (p.Glu135*)	Severe	Patient sufferes from spontaneous bruising and gingivorrhagia.Post-operative bleeding following cholecystectomy requiring no therapeutic intervention. Ovarian bruising following obstetric delivery.	Quelin et al 2009
421	F	French	38	Heterozygote		Not Reported	Bleeding following tooth extraction - requiring no therapeutic intervention. No spontaneous bleeding symptoms.	Quelin et al 2009
422	F	French	35	Heterozygote		Not Reported	Easy bruising	Quelin et al 2009

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.688T>C

p.Cys230Arg (Legacy AA No. 212)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

4

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Saunders et al 2005, Tiscia et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	Inheritance	Severity	Comments	Reference
41			Japanese		Homozygote	Severe		Morishita et al 2003 (Abstract)
234			UK Population	1	Homozygote	Not Reported		Mitchell et al 2006
542	25	M	Italian	34	Heterozygote	Not Reported	Asymptomatic	Tiscia et al 2017
543	55	F	Italian	34	Heterozygote	Not Reported	Asymptomatic	Tiscia et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.695A>C

p.His232Pro (Legacy AA No. 214)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

A>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
627	4	M	Indian	<1		Homozygote		Not Reported	No bleeding	Kawankar et al 2016

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.716T>C

p.Phe239Ser (Legacy AA No. 221)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

3

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Transient expression experiment revealed secretion of Phe239Ser FXI was significantly reduced compared with that of wild-type FXI. Morishita et al 2003 (Abstract), Okumura et al 2006

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Reference
47			Japanese			Compound heterozygote	c.1556insG	Severe	Morishita et al 2003 (Abstract)
423	43	M	Japanese	<3	7	Homozygote		Severe	Okumura et al 2006
424			Japanese			Compound heterozygote	c.1556insG	Not Reported	Kuroda et al 2005 (Abstract)

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.723C>G

p.Phe241Leu (Legacy AA No. 223)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

C>G

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

19

Allele Number *:

282784

Allele Frequency *:

0.000067

Variant Comments & Reference:

Asselta et al 2017

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.728C>T

p.Ser243Phe (Legacy AA No. 225)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

I

Allele Count *:

1

Allele Number *:

31376

Allele Frequency *:

0.000032

Variant Comments & Reference:

In single transient transfections, FXI-Phe243 levels in media are low compared with FXI-Wild-Type (WT). This appears to be due to reduced secretion, as FXI-Phe243 levels in lysates are comparable to FXI-WT. Co-transfection of FXI-WT with FXI-Phe243 results in reduced FXI in media compared with FXI-WT control, with little change in intracellular protein. Western blots of intracellular protein shows that FXI-Phe243 forms intracellular dimers similar to FXI-WT, indicating that poor secretion of this mutant is not due to a failure to form dimers. Kravtsov et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
144	34	M		22	22	Heterozygote		Not Reported	History of knee hemarthrosis and frequent epistaxis.	Kravtsov et al 2005
145				25	25	Heterozygote		Not Reported		Kravtsov et al 2005

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.730C>T

p.Gln244* (Legacy AA No. 226)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

3

Phenotype:

U

Allele Count *:

3

Allele Number *:

251356

Allele Frequency *:

0.000012

Variant Comments & Reference:

Okumura et al 2006

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	Inheritance	Other Variants	Severity	Comments	Reference
426	39	F	Japanese	<3	Heterozygote		Severe		Okumura et al 2006
427	62	M	Japanese	<3	Compound heterozygote	c.1253G>T (p.Gly418Val)	Severe		Okumura et al 2006
649	29	M	Taiwanese	<1	Compound heterozygote	c.1107C>A (p.Tyr369*)	Not Reported	Bleeding after dental extraction and hematuria (Grade II bleeding)	Lin et al 2020

Structural Interpretation:

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

c.731A>G

p.Gln244Arg (Legacy AA No. 226)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

A>G

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

None

Allele Count *:

601

Allele Number *:

282734

Allele Frequency *:

0.002126

Variant Comments & Reference:

This mutation is seen in compound heterzygosity but FXI:C is consistent with a partial deficiency and is likely a polymorphism. Sun et al 2001, O'Connell et al 2005, Wiewel-Verschueren et al 2017

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.738G>C

p.Trp246Cys (Legacy AA No. 228)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>C

Variant Effect:

Missense

No. of Patients Reported:

8

Phenotype:

I

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Introduction of an additional Cys residue within the third apple domain of FXI may result in mis-pairing of disulphide bridges resulting in an altered unstable conformation of the protein, targeting it for degradation within the cell. Also the mutant protein may be less efficiently secreted from the cell. Alhaq et al 1999

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Severity	Comments	Reference
61	68	F	Italian	2	Undetectable	Homozygote	Severe	Presented with cerebral thromboembolic event but no history of bleeding.	Alhaq et al 1999
124		M	Italian	40		Heterozygote	Mild	No history of Bleeding	Alhaq et al 1999
125		M	Italian	36		Heterozygote	Mild	No history of Bleeding	Alhaq et al 1999
126		F	Italian	50		Heterozygote	Mild	No history of Bleeding	Alhaq et al 1999
127		F	Italian	31		Heterozygote	Mild	No history of Bleeding	Alhaq et al 1999
128		F	Italian	3		Homozygote	Severe	No history of Bleeding	Alhaq et al 1999
129		F	Italian	6		Homozygote	Severe	No history of Bleeding	Alhaq et al 1999
130		F	Italian	53		Heterozygote	Mild	No history of Bleeding	Alhaq et al 1999

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.738G>A

p.Trp246* (Legacy AA No. 228)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>A

Variant Effect:

Nonsense

No. of Patients Reported:

19

Phenotype:

U

Allele Count *:

4

Allele Number *:

251324

Allele Frequency *:

0.000016

Variant Comments & Reference:

Saunders et al 2009, Wang et al 2019, Liu et al 2019, Xia 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
132		F	Chinese			Compound heterozygote	c.1202G>A (p.Trp401*)	Not Reported		Wu et al 2003 (Abstract)
133			Chinese			Heterozygote		Not Reported		Wu et al 2004 (Abstract)
617	32	F	Chinese	1		Compound heterozygote	c.137G>T (p.Cys46Phe)	Not Reported	Easy bruising and menorrhagia	Shao et al 2016
624	5	F	Chinese	<1		Compound heterozygote		Not Reported	Epistaxis - also carries A91fsX9 mutation	Shao et al 2016
640	32	F	Chinese	2	5.4	Compound heterozygote	c.938G>T (p.Ser313Ile)	Not Reported	Heavy menorrhagia and delayed wound healing	Wang et al 2019
642		F	Chinese	62	64.1	Heterozygote		Not Reported	No bleeding disorders	Wang et al 2019
644		F	Chinese	40	48.3	Heterozygote		Not Reported	No bleeding disorders	Wang et al 2019
645		F	Chinese	38	44.8	Heterozygote		Not Reported	No bleeding disorders	Wang et al 2019
652	58	M	Taiwanese	<1		Compound heterozygote	c.1107C>A (p.Tyr369*)	Not Reported	Gastrointestinal bleeding (Grade III bleeding)	Lin et al 2020
660		F				Compound heterozygote	c.1556G>C (p.Trp519Ser)	Not Reported	Reduced FXI activity and antigen levels to 6% and 10.7% of normal, respectively.	Liu et al 2019
661		F				Heterozygote		Not Reported		Liu et al 2019
662		F				Heterozygote		Not Reported		Liu et al 2019
663		F				Heterozygote		Not Reported		Liu et al 2019
667		F				Compound heterozygote	c.938G>T (p.Ser313Ile)	Not Reported	Reduced FXI activity and antigen levels to 10% and 15% of normal, respectively.	Xia et al 2020
668		F				Compound heterozygote	c.938G>T (p.Ser313Ile)	Not Reported	Reduced FXI activity and antigen levels to 2% and 11.5% of normal, respectively.	Xia et al 2020
669		M				Heterozygote		Not Reported		Xia et al 2020
670		F				Heterozygote		Not Reported		Xia et al 2020
671		F				Heterozygote		Not Reported		Xia et al 2020
679	4	M		<1		Compound heterozygote	c.841C>T (p.Gln281*)	Severe	Bruising	Zhang et al 2020

Structural Interpretation:

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

c.751C>T

p.Gln251* (Legacy AA No. 233)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

C>T

Variant Effect:

Nonsense

No. of Patients Reported:

1

Phenotype:

I

Allele Count *:

1

Allele Number *:

251356

Allele Frequency *:

0.000004

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
235			UK Population	<1	<3	Compound heterozygote	c.403G>T (p.Glu135*)	Severe		Mitchell et al 2006

Structural Interpretation:

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

c.755G>T

p.Arg252Ile (Legacy AA No. 234)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

0

Phenotype:

U

Allele Count *:

1

Allele Number *:

251340

Allele Frequency *:

0.000004

Variant Comments & Reference:

Bolton-Maggs et al 2003 (Abstract)

Patient Information: Show

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.755G>A

p.Arg252Lys (Legacy AA No. 234)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

1

Phenotype:

U

Allele Count *:

-

Allele Number *:

-

Allele Frequency *:

-

Variant Comments & Reference:

Replacement of hydrophilic basic Arg withhydrophilic basic Lys occurs in the last nucleotide of exon 7 and likely disrupts normal mRNA splicing. Duncan et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
428	26	F		41		Heterozygote		Not Reported	aPTT median = 39 seconds	Papagrigoriou et al 2006

Structural Interpretation:

Please click HERE for in-depth variant analysis.

c.756A>T

p.Arg252Ser (Legacy AA No. 234)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

A>T

Variant Effect:

Missense

No. of Patients Reported:

2

Phenotype:

U

Allele Count *:

1

Allele Number *:

251152

Allele Frequency *:

0.000004

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
236			UK Population	42		Heterozygote		Not Reported		Mitchell et al 2006
237			UK Population	38		Heterozygote		Not Reported		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).

Variant Comments & Reference:

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Structural Interpretation:

UNIQUE (Without Patient Data) :

EXCEL/CSV

TABULAR

MULTIPLE (With Patient Data) :

EXCEL/CSV

TABULAR