Factor XI Variant Database

In Depth Variant Analysis: c.992C>T (p.Thr331Ile)

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c.992C>T

p.Thr331Ile (Legacy AA No. 313)

Variant Type:

Point

Domain:

Apple 4

Codon Change:

C>T

Variant Effect:

Missense

No. of Patients Reported:

Phenotype:

Allele Count *:

Allele Number *:

Allele Frequency *:

Variant Comments & Reference:

Interestingly, this mutation is similar to the Thr51Ile conversion but occurs in Ap4. This Thr residue, Thr331, which is laid in the extended strand positioned after alpha-helix, is conserved in positions 60, 150, 240 and 331 of Apple 1, 2, 3 and 4 domains, respectively. The major role of Apple 4 is to mediate dimer formation of two identical polypeptide chains and the Thr331Ile change may distort the conformation of the Apple 4 domain and interfere with its function. Fard-Esfahani et al 2008

Patient Information: Show

Patient_ID	Age	Gender	Race	FXI:C%	FXI:Ag(%)	Inheritance	Other Variants	Severity	Comments	Reference
458	45	M	Iranian	<1		Homozygote		Severe	Moderate haemorrhage following oral surgery. Consanguineous parents.	Fard-Esfahani et al 2008

Residue Information:

	Name	Type	Cyclic	Size	Position	Hydrophobicity	Charge
Wild Type	Thr	-	acyclic	medium	surface	hydrophilic	neutral
Mutated	Ile	aliphatic	acyclic	large	buried	hydrophobic	neutral

Substitution Analysis:

Grantham Score : 89

PolyPhen-2 Prediction : Probably Damaging (SCORE: 0.996)

SIFT Prediction : Tolerated (SCORE: 0.16)

PROVEAN Prediction : Deleterious (SCORE: -3.308)

Structural Implications:

Thr331 is a buried residue (surface accessibility value = 0 ).

Thr331 is in a region of secondary structure within the FXI domains.

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

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