Factor XI Variant Database

In Depth Variant Analysis: c.3G>T (p.Met1Ile)

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c.3G>T

p.Met1Ile (Legacy AA No. -18)

Variant Type:

Point

Domain:

Signal Peptide

Codon Change:

G>T

Variant Effect:

Missense

No. of Patients Reported:

Phenotype:

Allele Count *:

Allele Number *:

31402

Allele Frequency *:

0.000032

Variant Comments & Reference:

Mutations affecting the ATG initiation codon have not been widely reported, and the loss of the initiation methionine in the Met1Ile variant was expected to be severely detrimental to protein synthesis and secretion. Expression studies show that no FXI is secreted, but surprisingly apparently normal (160 kDa) dimeric FXI was detected by western blot from cell lysates. Mitchell et al 2007

Patient Information: Show

Patient_ID	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Reference
214	UK Population	<1	<3	Compound heterozygote	c.438C>A (p.Cys146*)	Severe	Mitchell et al 2006
215	UK population			Heterozygote		Not Reported	Mitchell et al 2006
373		43		Heterozygote		Not Reported	Mitchell et al 2007

Residue Information:

	Name	Type	Cyclic	Size	Position	Hydrophobicity	Charge
Wild Type	Met	-	acyclic	large	buried	hydrophobic	neutral
Mutated	Ile	aliphatic	acyclic	large	buried	hydrophobic	neutral

Substitution Analysis:

Grantham Score : 10

PolyPhen-2 Prediction : Probably Damaging (SCORE: 0.969)

SIFT Prediction : Probably Damaging (SCORE: 0.00)

PROVEAN Prediction : Neutral (SCORE: -1.501)

Structural Implications:

Met1 is in a region on the surface of the FXI structure that is undefined. Hence the FXI structure and its JMOL applet are not shown below.

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