Factor XI Variant Database

In Depth Variant Analysis: c.1186C>T (p.Arg396Cys)

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c.1186C>T

p.Arg396Cys (Legacy AA No. 378)

Variant Type:

Point

Domain:

Serine Protease

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

Phenotype:

Allele Count *:

Allele Number *:

251486

Allele Frequency *:

0.000020

Variant Comments & Reference:

Expression studies indicate that this is a causative mutation (rather than a benign polymorphism -Germanos-Haddad et al 2003). FXI antigen assays confirm that FXI-Cys396 is secreted. FXI activity assays show FXI-Cys396 to have minimal activity, demonstrating that it is functionally inactive in an APTT-based assay. If, as is suggested in the Germanos-Haddad abstract, Arg396Cys is identified in the 'normal' lebanese population, thus leading to it being misassigned as a polymorphism, then it is possible that it is a common founder mutation. Mitchell et al 2007

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
245			UK Population	61	83	Heterozygote		Not Reported		Mitchell et al 2006
468		F		44		Heterozygote		Not Reported	Patient bleeds++, 'Slow wound healing' and menorrhagia.	Mitchell et al 2007

Residue Information:

	Name	Type	Cyclic	Size	Position	Hydrophobicity	Charge
Wild Type	Arg	basic	acyclic	large	surface	hydrophilic	postive
Mutated	Cys	-	acyclic	medium	buried	hydrophilic	neutral

Substitution Analysis:

Grantham Score : 180

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

SIFT Prediction : Tolerated (SCORE: 0.16)

PROVEAN Prediction : Neutral (SCORE: -0.966)

Structural Implications:

Arg396 is an exposed residue (surface accessibility value = 4 ).

Arg396 is in a random coil area of the FXI structure.

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

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