Factor XI Variant Database

In Depth Variant Analysis: c.901T>C (p.Phe301Leu)

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c.901T>C

p.Phe301Leu (Legacy AA No. 283)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

T>C

Variant Effect:

Missense

No. of Patients Reported:

Phenotype:

Allele Count *:

297

Allele Number *:

282824

Allele Frequency *:

0.001050

Variant Comments & Reference:

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

Patient Information: Show

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

Residue Information:

	Name	Type	Cyclic	Size	Position	Hydrophobicity	Charge
Wild Type	Phe	aromatic	cyclic	large	buried	hydrophobic	neutral
Mutated	Leu	aliphatic	acyclic	large	buried	hydrophobic	neutral

Substitution Analysis:

Grantham Score : 22

PolyPhen-2 Prediction : Probably Damaging (SCORE: 1.000)

SIFT Prediction : Probably Damaging (SCORE: 0.00)

PROVEAN Prediction : Deleterious (SCORE: -3.073)

Structural Implications:

Phe301 is a buried residue (surface accessibility value = 0 ).

Phe301 is in a region of secondary structure within the FXI domains.

The DSSP assignment for this residue is ... E.

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