SCN1A mutation database!

Electrophysiological studies on SCN1A mutations list

Total items found: 55

Number	Nucleotide change	Protein change	Location	Phenotype	Functional defect type	Details of the major biophysical abnormalities.	Reference
1	c.434T>C	p.Met145Thr(M145T)	DIS1	PEFS+ ^f	pLOF	60% reduction of current density, 10-mV positive (hypoexcitable) shift of activation curve.	Mantegazza M.2005
2	c.530G>A	p.Gly177Glu(G177E)	DIS2-S3	SMEI	LOF	No measurable sodium current.	Ohmori I.2006
3	c.563A>T	p.Asp188Val	DIS2-S3	GEFS+ ^f	IE	Increased resistance to cumulative inactivation during high frequency activation, indirect evidence of increased excitability.	Cossette P.2003
4	c.664C>T	p.Arg222X(R222X)	DIS4	SMEI	LOF	Do not generate Na+ current; slow down recovery from fast inactivation.	Bechi G.2012
5	c.680T>G	p.Ile227Ser(I227S)	DIS4	SMEI	LOF	No measurable sodium current.	Ohmori I.2006
6	c.787C>G	p.Leu263Val(L263V)	DIS5	FHM+EP	GOF	Exhibited gain-of function features, including delayed entry into, as well as accelerated recovery from, fast inactivation; depolarizing shifts in the steady-state voltage dependence of fast and slow inactivation; increased persistent current; and delayed entry into slow inactivation.	Kahlig KM.2008
7	c.902A>G	p.Asn301Ser(N301S)	DIS5-S6	Artificial	LOF	No measurable sodium current	Chen YJ.2014
8	c.1178G>A	p.Arg393His(R393H)	DIS5-S6	SMEI	LOF	No measurable sodium current.	Ohmori I.2006
9	c.1276T>A	p.Tyr426Asn(Y426N)	DI-DII (D-linkers)	SMEI	pLOF	Reduced current density, reduced channel availability by negative shift of inactivation and slower recovery from inactivation.	Ohmori I.2006
10	c.2134C>T	p.Arg712X(R712X)	DI-DII (D-linkers)	SMEI	LOF	Extremely small Na+ currents, generate non-functional channel.	Sugawara T.2003
11	c.2422A>T	p.Thr808Ser(T808S)	DIIS2	ICEGTC	IE	Increased current density, delayed both onset and recovery from slow inactivation.	Rhodes TH.2005
12	c.2575C>T	p.Arg859Cys(R859C)	DIIS4	GEFS+ ^f	DE	Hypoexcitable (positive) shift of activation, slower recovery from slow inactivation, lower levels of current.	Barela AJ.2006
13	c.2576G>A	p.Arg859His(R859H)	DIIS4	PEFS+ ^f	G-LOF	Increased persistent current and slower inactivation rate constant; reduction in voltage dependent steady state channel availability and a delayed recovery from fast inactivation.	Volkers L.2011
14	c.2589+3A>T	p.Val806_Leu863del(V806_L863del)	DIIS4	SMEI	LOF	No measurable sodium current.	Liu Y.2013
15	c.2593C>G	p.Arg865Gly(R865G)	DIIS4	SMEI	G-LOF	A large increase in persistent current, and a hyperpolarized shift in the voltage dependence of activation in combination with the unaltered voltage dependence of inactivation; slower recovery from inactivation.	Volkers L.2011
16	c.2624C>T	p.Thr875Met(T875M)	DIIS4	PEFS+ ^f	G-LOF	Small persistent current. Enhanced fast and slow inactivation that may result in reduced current density during long depolarization or repetitive stimulation.	Lossin C.2002; Alekov AK.2001; Spampanato J.2001
17	c.2705T>G	p.Phe902Cys(F902C)	DIIS5	SMEI	LOF	No measurable sodium current.	Rhodes TH.2004
18	c.2817C>G	p.His939Gln(H939Q)	DIIS5-S6	SMEI	LOF	No measurable sodium current.	Ohmori I.2006
19	c.2836C>T	p.Arg946Cys(R946C)	DIIS5-S6	SMEI	LOF	No measurable sodium current.	Volkers L.2011
20	c.2837G>A	p.Arg946His(R946H)	DIIS5-S6	PEFS+	LOF	No measurable sodium current .	Liao WP.2010
21	c.2875T>C	p.Cys959Arg(C959R)	DIIS5-S6	SMEI	LOF	No measurable sodium current.	Ohmori I.2006
22	c.2935G>A	p.Gly979Arg(G979R)	DIIS6	ICEGTC	LOF	No measurable sodium current.	Rhodes TH.2005; Sugawara T.2003
23	c.2948T>C	p.Val983Ala(V983A)	DIIS6	ICEGTC	pLOF	Reduced current density, hypoexcitable (positive) shift of activation, reduced channel availability by negative shift of inactivation and positive shift of activation. Possible increased channel availability suggested by delayed onset and faster recovery of slow inactivation (less direct).	Rhodes TH.2005
24	c.2954A>T	p.Asn985Ile(N985I)	DIIS6	SMEI	LOF	Extremely small Na+ currents, generate non-functional channel.	Sugawara T. 2003
25	c.2956C>T	p.Leu986Phe(L986F)	DIIS6	SMEI	LOF	No measurable sodium current.	Lossin C.2003
26	c.3032A>T	p.Asn1011Ile(N1011I)	DII-DIII (D-linkers)	ICEGTC	pLOF	Reduced current density, negative shift of inactivation.	Rhodes TH.2005
27	c.3521C>G	p.Thr1174Ser (T1174S)	DII-DIII (D-linkers)	PEFS+ ^f	G-LOF	Increase of persistent current; positive shift of the activation curve and deceleration of recovery from fast inactivation, consistent with loss of function.	Cest
28	c.3610T>C	p.Trp1204Arg(W1204R)	DII-DIII (D-linkers)	GEFS+ ^f	GOF	Small persistent current, hyperexcitable (negative) shift of activation curve, hyperexcitable shift of window current (negative shift in both activation and inactivation curve).	Lossin C.2002; Spampanato J.2003
29	c.3733C>T	p.Arg1245X(R1245X) (Arg1234X,R1234X)	DIII S1-S2	SMEI	LOF	Do not generate Na+ current; slow down recovery from fast inactivation.	Bechi G.2012
30	c.3867_3869delCTT	p.Phe1289del(F1289del)	DIIIS3	SMEB	LOF	No measurable sodium current.	Ohmori I.2006
31	c.4057G>C	p.Val1353Leu(V1353L)	DIIIS5	PEFS+ ^f	LOF	No measurable sodium current.	Lossin C.2003
32	c.4219C>T	p.Arg1407X (R1396X)	DIIIS5-S6	SMEI	LOF	Extremely small Na+ currents, generate non-functional channel.	Sugawara T.2003
33	c.4465C>A	p.Gln1489Lys(Q1489K)	DIII-DIV	FHM ^f	pLOF	Increased persistent current but also enhanced entry into slow inactivation as well as delayed recovery from fast and slow inactivation, thus resulting in a predominantly loss-of-function phenotype further demonstrated by a greater loss of channel availability during repetitive stimulation.	Kahlig KM.2008
34	c.4723C>T	p.Arg1575Cys(R1575C)	DIVS2	Rasmussen encephalitis ^f	GOF	Exhibited increased channel availability and an increased persistent sodium current in comparison to the wild-type.	Ohmori I.2008
35	c.4831G>T	p.Val1611Phe(V1611F)	DIVS3	GEFS+ ^f	GOF	Small persistent current, hyperexcitable shift of window current (negative shift in both activation and inactivation curve).	Rhodes TH.2005
36	c.4894C>T	p.Pro1632Ser(P1632S)	DIVS3-S4	ICEGTC	G-LOF	Moderate persistent current. Reduced window current (channel availability) by greater negative shift of inactivation than the negative shift of activation, reduced channel availability by greater delaying in recovery than in onset of slow inactivation.	Rhodes TH.2005
37	c.4942C>T	p.Arg1648Cys(R1648C)	DIVS4	SMEI	G-LOF	Bigger persistent current comparing with R1648H. Hypoexcitable (positive) shift of activation, reduced channel availability by negative shift of inactivation and positive shift of activation.	Rhodes TH.2005
38	c.4943G>A	p.Arg1648His(R1648H)	DIVS4	GEFS+ ^f	G-LOF	Moderate persistent current,slowed inactivation and increased recovery from inactivation Enhanced slow inactivation that may result in reduced current density during long depolarization or repetitive stimulation.	Rhodes TH.2004; Lossin C.2002; Spampanato J.2001; Alekov A.2000
39	c.4946T>A	p.Leu1649Gln(L1649Q)	DIVS4	FHM	LOF	Failed to generate measurable whole-cell current.	Kahlig KM.2008
40	c.4968C>G	p.Ile1656Met(I1656M)	DIVS4	GEFS+ ^f	DE	Hypoexcitable (positive) shift of activation and negative shift of inactivation.	Lossin C. 2003
41	c.4969C>T	p.Arg1657Cys(R1657C)	DIVS4	SMEI ^f	G-LOF	Reduced current density and hypoexcitable (positive) shift of activation. Accelerated recovery from fast and slow inactivation.	Lossin C. 2003
42	c.4982T>C	p.Phe1661Ser(F1661S)	DIVS4-S5(V-sensor)	SMEI	G-LOF	Big persistent current. Reduced current density, impaired recovery from slow inactivation.	Rhodes TH.2004
43	c.5020G>C	p.Gly1674Arg(G1674R)	DIVS5	SMEI	LOF	No measurable sodium current.	Rhodes TH.2004
44	c.5054C>T	p.Ala1685Val(A1685V)	DIVS5	PEFS+ ^f	LOF	No measurable sodium current.	Sugiura Y.2012
45	c.5054C>A	p.Ala1685Asp(A1685D)	DIVS5	SMEI	LOF	The mutant channel with and without b1 subunit did not conduct any sodium currents.	Sugiura Y.2012
46	c.5126C>T	p.Thr1709Ile(T1709I)	DIVS5-S6	ICEGTC ^f	LOF	No measurable sodium current.	Rhodes TH.2005
47	c.5246G>A	p.Gly1749Glu(G1749E)	DIVS5-S6	SMEI	pLOF	Reduced current density, faster onset of slow inactivation.	Rhodes TH.2004
48	c.5295T>A	p.Phe1765Leu(F1765L)	DIVS6	PEFS+	LOF	No measurable sodium current.	Liao WP.2010
49	c.5422T>C	p.Phe1808Leu(F1808L)	C-terminal	ICEGTC	G-LOF	Big persistent current. Reduced current density, reduced window current (channel availability) by greater negative shift of inactivation than the negative shift of activation.	Rhodes TH.2005
50	c.5492T>C	p.Phe1831Ser(F1831S)	C-terminal	SMEI	pLOF	Apparent reduction of peak current.	Sugawara T. 2003
51	c.5555T>C	p.Met1852Thr(M1852T)	C-terminal	SMEI ^f	pLOF	Reduced current density that could be partially rescued, with trafficking defect involved.	Rusconi R.2007
52	c.5596G>T	p.Asp1866Tyr(D1866Y)	C-Terminal	GEFS+ ^f	GOF	Positive shift of fast inactivation due to reduced association with	Spampanato J.2004
53	c.5674C>T	p.Arg1892X (R1881X)	C-Terminal	SMEI	pLOF	Showed a drastic attenuation of the peak Na+ current, small yet detectable sodium currents.	Sugawara T. 2003
54	c.5726C>T	p.Thr1909Ile(T1909I)	C-terminal	SMEI	G-LOF	Reduced current density. Small persistent current.	Ohmori I.2006
55	c.5779A>G	p.Arg1927Gly(R1927G) (Arg1916Gly,R1916G)	C-terminal	GEFS+ ^f	pLOF	Loss of function caused by folding defects that can be rescued by molecular interactions with associated proteins and drugs.	Rusconi R.2009

Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China

Collaborative Innovation Center for Neurogenetics and Channelopathies, Guangzhou 510260, China.