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Full List of Variants: 272 unique variants retrieved (displaying 50 entries per page). Scroll down to navigate to the next page(s).
Terms with a '*' next to them are explained on the Help Page .
c.1718G>A
p.Gly573Glu (Legacy AA No. 555)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>A
Variant Effect:
Missense
No. of Patients Reported:
2
Phenotype:
II
Allele Count *:
2
Allele Number *:
251370
Allele Frequency *:
0.000008
Variant Comments & Reference:
Normal amount of mutant protein secreted from BHK cells. Experimental data indicates the mutation changes the conformation of the unoccupied active site of FXIa. When compared with wild type, FXI-Glu573 activates FIX at a greatly reduced rate. Modelling indicates side chain of Glu573 alters electrostatic charge around active site and interferes with the interaction between FXI and FIX and antithrombin. Zivelin et al 2001 (Abstract), Zivelin et al 2004, Schmidt et al 2004Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1721A>C
p.Asp574Ala (Legacy AA No. 556)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
A>C
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
U
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Kawankar et al 2016Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1721A>G
p.Asp574Gly (Legacy AA No. 556)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
A>G
Variant Effect:
Missense
No. of Patients Reported:
0
Phenotype:
U
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Castaman et al 2007 (ISTH Abstract)Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1741T>C
p.Cys581Arg (Legacy AA No. 563)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
T>C
Variant Effect:
Missense
No. of Patients Reported:
2
Phenotype:
U
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Disrupts Cys553–Cys581 bond. Colakoglu et al 2018Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1742G>T
p.Cys581Phe (Legacy AA No. 563)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>T
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
U
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Saunders et al 2009Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1760G>C
p.Trp587Ser (Legacy AA No. 569)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>C
Variant Effect:
Missense
No. of Patients Reported:
2
Phenotype:
I
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Co-transfection with wild-type and mutant protein reduces wild-type secretion about 50% - non-secretable mutant protein monomers trap wild-type polypeptides within cells through homodimer formation, resulting in lower FXI levels in plasma. Mutant protein is not expressed in 293 kidney fibroblasts. Gailani et al 2001 (Abstract B), Kravtsov et al 2004Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1775T>C
p.Ile592Thr (Legacy AA No. 574)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
T>C
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
U
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Esteban et al 2017Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1778C>T
p.Thr593Met (Legacy AA No. 575)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
C>T
Variant Effect:
Missense
No. of Patients Reported:
8
Phenotype:
II
Allele Count *:
10
Allele Number *:
251488
Allele Frequency *:
0.000040
Variant Comments & Reference:
Expression studies confirm that Thr593Met is a type II (CRM+) variant with a loss of functional activity most likely due to disruption of the catalytic domain. Thr593 in the catalytic domain is highly conserved. Molecular modeling predicts that the introduction of Met at position 593 results in the formation of a new hydrogen bond with Ser575, one of the residues that make up the serine protease catalytic triad in the FXI protein. Mitchell et al 2007Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1782C>A
p.Ser594Arg (Legacy AA No. 576)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
C>A
Variant Effect:
Missense
No. of Patients Reported:
3
Phenotype:
II
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Ser594 partially projects into the substrate binding cleft formed between the two subdomains of the SP domain. The replacement by Arg594 is expected to block the binding of substrate to the cleft. This interpretation was supported by energy minimization which showed that no conformational changes had occurred in the SP domain. O'Connell et al 2005Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1786G>A
p.Gly596Cys (Legacy AA No. 578)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>A
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
I
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Gly596Cys causes the introduction of a sulfhydryl group in the catalytic domain of FXI. Castaman et al 2008Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1789G>A
p.Glu597Lys (Legacy AA No. 579)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>A
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
U
Allele Count *:
1
Allele Number *:
251490
Allele Frequency *:
0.000004
Variant Comments & Reference:
Glu597Lys affects overall protein charge. A given patient presented with low levels of FXI activity (15 iu/dL), either due to an undetected mutation in the experimental procedure or due to the fact that Glu597Lys is a dominant mutation that can exert a negative effect on secretion of wild-type FXI. Such dominant mutants have already been described: Trp587Ser, Thr593Met and Ser594Arg. Interestingly, the four mutations are located with in the same 10-amino acid strand, suggesting a critical role for this segment in the dimerisation process. Quelin et al 2006Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1796G>A
p.Cys599Tyr (Legacy AA No. 581)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>A
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
U
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Disrupts the Cys571-Cys599 bond in the catalytic domain of FXIa. Esteban et al 2017Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1797T>A
p.Cys599* (Legacy AA No. 581)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
T>A
Variant Effect:
Nonsense
No. of Patients Reported:
2
Phenotype:
II
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
This mutation disrupts the Cys571-Cys599 bond in the catalytic domain of FXIa. In addition this disulphide bond is located near the third amino acid (Ser575) implicated in the catalytic triad of FXIa, so this disruption may interfere with FXIa catalytic activity. Mutation also results in heterodimer trapping. Quelin et al 2004, Duga & Salomon 2013Structural Interpretation:
Structural analysis cannot be performed on this (Point | Nonsense) variant. c.1812G>T
p.Arg604= (Legacy AA No. 586)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>T
Variant Effect:
Silent
No. of Patients Reported:
0
Phenotype:
None
Allele Count *:
17400
Allele Number *:
282854
Allele Frequency *:
0.061516
Variant Comments & Reference:
Polymorphism. Zivelin et al 2002, Wiewel-Verschueren et al 2017Structural Interpretation:
Structural analysis cannot be performed on this (Point | Silent) variant. c.1822T>C
p.Tyr608His (Legacy AA No. 590)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
T>C
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
U
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Tyr608His lies near the catalytic triad and the change to basic His may interfere with the appropriate conformation of the protease domain. Fard-Esfahani et al 2008Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1824C>A
p.Tyr608* (Legacy AA No. 590)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
C>A
Variant Effect:
Nonsense
No. of Patients Reported:
2
Phenotype:
U
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Bolton-Maggs et al 2003 (Abstract)Structural Interpretation:
Structural analysis cannot be performed on this (Point | Nonsense) variant. c.1832T>G
p.Val611Gly (Legacy AA No. 593)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
T>G
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
I
Allele Count *:
1
Allele Number *:
251478
Allele Frequency *:
0.000004
Variant Comments & Reference:
Unpublished DataStructural Interpretation:
Please click HERE for in-depth variant analysis. c.1839G>A
p.Glu613= (Legacy AA No. 595)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>A
Variant Effect:
Silent
No. of Patients Reported:
0
Phenotype:
None
Allele Count *:
15421
Allele Number *:
282820
Allele Frequency *:
0.054526
Variant Comments & Reference:
Polymorphism. Zivelin et al 2002, Wiewel-Verschueren et al 2017Structural Interpretation:
Structural analysis cannot be performed on this (Point | Silent) variant. c.1843G>A
p.Val615Met (Legacy AA No. 597)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
G>A
Variant Effect:
Missense
No. of Patients Reported:
0
Phenotype:
None
Allele Count *:
105
Allele Number *:
282852
Allele Frequency *:
0.000371
Variant Comments & Reference:
Polymorphism. Wiewel-Verschueren et al 2017Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1849T>G
p.Trp617Arg (Legacy AA No. 599)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
T>G
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
I
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Saunders et al 2009Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1853T>C
p.Ile618Ser (Legacy AA No. 600)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
T>C
Variant Effect:
Missense
No. of Patients Reported:
3
Phenotype:
I
Allele Count *:
-
Allele Number *:
-
Allele Frequency *:
-
Variant Comments & Reference:
Bolton-Maggs et al 2003 (Abstract)Structural Interpretation:
Please click HERE for in-depth variant analysis. c.1856T>C
p.Leu619Pro (Legacy AA No. 601)
Variant Type:
Point
Domain:
Serine Protease
Codon Change:
T>C
Variant Effect:
Missense
No. of Patients Reported:
1
Phenotype:
I
Allele Count *:
1
Allele Number *:
251354
Allele Frequency *:
0.000004