Factor X Variant Database

In-Depth Variant Analysis: c.1012G>A (p.Val338Met)

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c.1012G>A

p.Val338Met (Legacy AA No. 298)

Variant Type:

Point

Domain:

Serine protease

Location:

Exon 8

Variant Effect:

Missense

Codon Change:

G>A

No. of Patients Reported:

Phenotype:

Allele Count *:

Allele Number *:

282434

Allele Frequency *:

0.000007

Variant Comments & Reference:

Variant induces a conformational change to minimise steric clash with bulky Met residue, resulting in misfolding of FX (Stuart Factor).

Patient Information: Show

Patient_ID	Age (Yrs)	Gender	Race	FX:C(%)	FX:C (IU/dl)	FX:Ag(%)	FX:Ag (IU/dl)	Inheritance	Other Variants	Severity	Comments	Reference
119	11	M	Caucasian		<1		66	Heterozygous	c.166G>A (p.Glu56Lys)	Severe	Hemarthrosis of knee joint. Related to pa_id: 120, 121 & 122.	Ingerslev et al 2007
120	8	F	Caucasian		<1		37	Heterozygous	c.166G>A (p.Glu56Lys)	Severe	Risk of intracranial bleeding during birth. Mucosal and joint bleeds. Related to pa_id: 119, 121 & 122.	Ingerslev et al 2007
121		F	Caucasian		47		89	-		Asymptomatic	Asymptomatic. Related to pa_id: 119 & 120.	Ingerslev et al 2007
124	32	F	British		<1		5	Heterozygous	c.1151_1167delACGTGGACCGCAACAG ( p.Tyr384LeufsTer57)	Severe	Spontaneous/ hemorrhagic bleeding.	Mitchell et al 2019
345	36	M	Italian					Homozygous		Severe	Epistaxis, hematomas, hemarthrosis, severe anemia.	Hougie, Barrow & Graham 1957
45				<1		2		Heterozygous	c.1151_1167delACGTGGACCGCAACAG ( p.Tyr384LeufsTer57)	Moderate	Significant hemorrhagic symptoms. Related to pa_id: 46, 47, 48 & 49.	Millar et al 2000
46		F		41		38		Heterozygous		Not Reported	Related to pa_id:45, 48 & 49.	Millar et al 2000
48				28		34		Heterozygous		Not Reported	Relaed to pa_id: 45, 46, 47 & 49.	Millar et al 2000
49				41		39		Heterozygous		Not Reported	Related to pa_id: 45, 46, 47 & 48.	Millar et al 2000

Residue Information:

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

Substitution Analysis:

Grantham Score : 21

PolyPhen-2 Prediction : Probably Damaging (SCORE: 1.000)

SIFT Prediction : Probably Damaging (SCORE: 0.00)

PROVEAN Prediction : Neutral (SCORE: -2.386)

Structural Implications:

Val338 is a buried residue (surface accessibility value = 0 ).

Val338 is in a region of secondary structure within the FX domains.

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

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