Variant Comments & Reference:

Mutant protein is expressed in 293 human kidney fibroblasts. Activated mutant has a modest catalytic defect in functional assays. The basis of catalytic defect that results from Pro538Leu alteration is due to subtle alterations in the oxyanion hole, which develops during conversion of zymogen to active enzyme, and results in a ~3.5-fold decrease in catalytic efficiency, consistent with the 70-80% loss of activity noted in conventional coagulation assays. Thus, Pro538 is important in maintaining the normal conformation of the FXI active site. Pro538 is conserved in FX and FVII, and its mutation in both these other proteins also causes Type II phenotypes.This variant was not activated by FXIIa. Gailani et al 2001 (Abstract), Gailani et al 2007, Saunders et al 2009, Esteban et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
83	8on	M		34		Heterozygote		Not Reported	Prolonged bleeding from a scratch on the nose that required cautery.	Gailani et al 2001 Abstract B
179	65	F		43	90	Heterozygote		Not Reported	Patient also has von Willebrand disease	Hill et al 2005
180	47	F		48		Heterozygote		Not Reported	Easy bruising, menorrhagia	Hill et al 2005
205		M	French	30		Compound heterozygote	c.783G>C (p.Glu261Asp)	Not Reported		Quelin et al 2005
256			UK Population	48	80	Heterozygote		Not Reported		Mitchell et al 2006
257			UK Population	53		Heterozygote		Not Reported		Mitchell et al 2006
494		F		50	74	Heterozygote		Not Reported	No bleeding Hx.	Quelin et al 2009
599	71	M	Spanish	20		Homozygote		Not Reported		Esteban et al 2017
600	88	F	Spanish	59		Heterozygote		Not Reported		Esteban et al 2017

Structural Interpretation:

Please click HERE for in-depth variant analysis.