Factor XI Variant Database

In Depth Variant Analysis: c.1247G>A (p.Cys416Tyr)

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c.1247G>A

p.Cys416Tyr (Legacy AA No. 398)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

G>A

Variant Effect:

Missense

No. of Patients Reported:

Phenotype:

Allele Count *:

Allele Number *:

251468

Allele Frequency *:

0.000016

Variant Comments & Reference:

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

Patient Information: Show

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

Residue Information:

	Name	Type	Cyclic	Size	Position	Hydrophobicity	Charge
Wild Type	Cys	-	acyclic	medium	buried	hydrophilic	neutral
Mutated	Tyr	aromatic	cyclic	large	surface	hydrophobic	neutral

Substitution Analysis:

Grantham Score : 194

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

SIFT Prediction : Probably Damaging (SCORE: 0.00)

PROVEAN Prediction : Deleterious (SCORE: -8.790)

Structural Implications:

Cys416 is a buried residue (surface accessibility value = 0 ).

Cys416 is in a region of secondary structure within the FXI domains.

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

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