Variant Comments & Reference:

The novel missense mutation FXI Lys536Asn leads to the replacement of the Lys536 which is part of a LxxxxxPxxxxxxC motif (x-variable amino acid) that occurs in several subfamilies of serine proteases. Although this motif is highly conserved between FXI and pre-kallikrein (86% sequence identity), the Lys536 is not conserved. On the other hand, this residue is conserved in human, murine and bovine FXI indicating that this is a FXI-specific amino acid. A molecular model of FXI predicts that the side-chain of this residue is on the surface of the molecule, possibly H-bonded to W515. Replacement of the positively charged lysine side chain by the smaller, neutral side chain of asparagine may interfere with the folding of the FXI molecule and/or secretion, leading to low antigen level. Alternatively, the secreted FXI variant may have a shortened plasma half-life. Ventura et al 2000, Esteban et al 2017

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
54		F	Portuguese	1	5	Compound heterozygote	c.1026G>T (p.Gly342=)	Severe	Excessive bleeding after dental extraction. Menorrhagia.	Ventura et al 2000
55		F	Portuguese	1	12	Compound heterozygote	c.1026G>T (p.Gly342=)	Severe	Non-bleeder.	Ventura et al 2000
95		M	Portuguese			Heterozygote		Mild		Ventura et al 2000
601	47	F	Spanish	3		Compound heterozygote	c.1796G>A (p.Cys599Tyr)	Not Reported		Esteban et al 2017

Structural Interpretation:

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