Factor XI Variant Database

In Depth Variant Analysis: c.728C>T (p.Ser243Phe)

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c.728C>T

p.Ser243Phe (Legacy AA No. 225)

Variant Type:

Point

Domain:

Apple 3

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

Phenotype:

Allele Count *:

Allele Number *:

31376

Allele Frequency *:

0.000032

Variant Comments & Reference:

In single transient transfections, FXI-Phe243 levels in media are low compared with FXI-Wild-Type (WT). This appears to be due to reduced secretion, as FXI-Phe243 levels in lysates are comparable to FXI-WT. Co-transfection of FXI-WT with FXI-Phe243 results in reduced FXI in media compared with FXI-WT control, with little change in intracellular protein. Western blots of intracellular protein shows that FXI-Phe243 forms intracellular dimers similar to FXI-WT, indicating that poor secretion of this mutant is not due to a failure to form dimers. Kravtsov et al 2005

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
144	34	M		22	22	Heterozygote		Not Reported	History of knee hemarthrosis and frequent epistaxis.	Kravtsov et al 2005
145				25	25	Heterozygote		Not Reported		Kravtsov et al 2005

Residue Information:

	Name	Type	Cyclic	Size	Position	Hydrophobicity	Charge
Wild Type	Ser	-	acyclic	small	surface	hydrophilic	neutral
Mutated	Phe	aromatic	cyclic	large	buried	hydrophobic	neutral

Substitution Analysis:

Grantham Score : 155

PolyPhen-2 Prediction : Probably Damaging (SCORE: 0.997)

SIFT Prediction : Probably Damaging (SCORE: 0.00)

PROVEAN Prediction : Neutral (SCORE: -2.432)

Structural Implications:

Ser243 is a buried residue (surface accessibility value = 1 ).

Ser243 is in a random coil area of the FXI structure.

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

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