Andersen Syndrome: Locus table - Andersen syndrome: synopsis

OMIM: 170390

KCNJ2: cDNA; Gene: 3759; Unigene

Protein: AAF73241 -

Nucleotide Change	Amino Acid Change	Mutation Type	Functional Effect		QTc (ms)	Arrhythmia	Age of Onset	References
C199T	R67W	Missense	Dominant-negative; PIP2 binding		normal	Polymorphic VT;	12	Andelfinger et al, 2002; Donaldson et al. 2003; Haruna I et al 2007
G200A	R67Q	Missense	Reduced IK1; no dominant negative		normal	isolated PCVs, polymorphic VT	13	Haruna et al 2007; Eckhardt et al. 2007
T202C	Y68D	Missense	N7A		N/A	N/A		Davies et al. 2005
A212T	D71V	Missense	Dominant-negative		513	None	N/A	Plaster et al, 2001
G211A	D71N	Missense	PIP2 binding		546	Bigeminy, polymorphic VT		Donaldson et al. 2003
	T74A	Missense	Trafficking defect					Zhang et al. 2005; Ballester et al 2006
A223G	T75A	Missense	Dominant-negative		444(1)	none	N/A	Fostad et al 2004
C224G	T75R	Missense	PIP2 binding		470	Bigeminy, bidirectional VT		Donaldson et al. 2003
C224T	T75M	Missense	PIP2binding		490	Bidirectional VT	N/A	Tani I et al. 2007
A233G	D78G	Missense			N/A	N/A (periodic paralysis)	8	Davies et al. 2005
C244T	R82W	Missense			440	Ventricular ectopies, syndope	9	Tester et al 2006
G245A	R82Q	Missense	Dominant negative		480	Bidirectional VT (with periodic paralysis)	15	Davies et al. 2005
513-524del	95-8del	Deletion	Dominant-negative; trafficking defect		475	Bigeminy, polymorphic VT	12	Tristani-Firouzi at al, 2002
C301T	C101R	Missense	-					Zhang et al. 2005
T368G	V123G	Missense	N/A		N/A	none	18	Davies et al. 2005
-	S136F	Missense	Dominant-negative		500	Bigeminy	N/A	Tristani-Firouzi at al, 2002
G431C	G144A	Missense	Trafficking defect					Zhang et al. 2005; Ballester et al 2006
G430A	G144S	Missense	Dominant-negative		480	Bidirectional VT	N/A	Tristani-Firouzi at al, 2002; Haruna et al 2007
G437A	G146D	Missense	PIP2 binding		normal	none		Donaldson et al. 2003
-	163-164delFQ	Deletion	M2 region-functional data N.A.		456(1)	none	N/A	Fostad et al 2004
C557T	P186L	Missense	Dominant-negative; PIP2 binding		RBBB	Polymorphic VT	N/A	Tristani-Firouzi at al, 2002
G566T	R189I	Missense	PIP2 binding		N/A	N/A		Donaldson et al. 2003
	T192A	Missense	Haplo-insufficiency; PIP2 binding		680	Bigeminy, frequent PVC	12	Ai et al, 2002; Haruna et al 2007
A644G	G215D	Missense	Dominant Negative		480 (excluding prominent U waves)	VT (inducible at PES)	8	Hosaka et al 2003; Haruna et al 2007
A646C	N216H	Missense	Dominant-negative; PIP2 binding		470	Bidrectional VT and non-fatal cardiac arrest	4	Tristani-Firouzi at al, 2002
T650C	L217P	Missense	Dominant negetive		N/A	N/A	5	Davies et al. 2005
C652T	R218W	Missense	Dominant-negative; PIP2 binding		560 1st degree AV block	Bigeminy, torsades, non-fatal cardiac arrest.	10	Tristani-Firouzi at al, 2002; Donaldson et al. 2003
C652T	R218W	Missense	Dominant-negative; PIP2 binding		488	Bigeminy, polymorphic VT	13	Plaster et al, 2001; Haruna et al 2007
G653A	R218Q	Missense	Dominant-negative; PIP2 binding		469	None	15	Tristani-Firouzi at al, 2002; Haruna et al 2007
G679T	V227F	Missense	-		405	Non sustained polymorphic VT	17	Tester et al 2006
G899A	G300D	Missense	PIP2 binding		N/A	Bigeminy		Donaldson et al. 2003
G899T	G300V	Missense	Dominant-negative; PIP2 binding		480	Bigeminy, polymorphic VT	19	Tristani-Firouzi at al, 2002; Haruna et al 2007
G904A	V302M	Missense	Dominant-negative; PIP2 binding; trafficking defect		RBBB	Bigeminy	N/A	Tristani-Firouzi at al, 2002
G907A	E303K	Missense	Dominant-negative; PIP2 binding		495	Frequent PVCs	N/A	Tristani-Firouzi at al, 2002
A913G	T305A	Missense	Mild dominant negative effect		N/A	Asymptomatic/Ventricular ectopy Polymorphic VT	11	Eckhardt et al. 2007
-	M307I	Missense	PIP2 binding. trafficking defect		N/A	Frequent PVCs	16	Choi et al 2007
C926T	T309I	Missense	-		N/A	N/A	13	Haruna et al 2007
C934T	R312C	Missense	PIP2 binding		450 (bordeline)	none		Donaldson et al. 2003
1393-944del	314-5del	Deletion	Dominant-negative; PIP2 binding; trafficking defect		471	Torsades, monomorphic VT	4	Tristani-Firouzi at al, 2002

VT = Ventricular Tachycardia; HR= heart rate; bpm = beats/min; QTc = heart rate corrected QT interval; N/A= not available; RBBB= right bundle branch block (precludes accurate measurement of QTc); PVC= premature ventricular contraction; VT= ventricular tachycardia; AV= atrioventricular.PES = Programmed Electrical Stimulation

⁽¹⁾ No dysmorphic features suggesting Andersen syndrome were present.