Electrophysiological studies on SCN1A mutations list
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Total items found: 55
NumberNucleotide changeProtein changeLocationPhenotypeFunctional defect type Details of the major biophysical abnormalities.Reference
1c.434T>Cp.Met145Thr(M145T)DIS1PEFS+ fpLOF 60% reduction of current density, 10-mV positive (hypoexcitable) shift of activation curve.Mantegazza M.2005
2c.530G>Ap.Gly177Glu(G177E)DIS2-S3SMEI LOF No measurable sodium current.Ohmori I.2006
3c.563A>Tp.Asp188Val(D188V)DIS2-S3GEFS+ fIE Increased resistance to cumulative inactivation during high frequency activation, indirect evidence of increased excitability.Cossette P.2003
4c.664C>Tp.Arg222X(R222X)DIS4(V-sensor)SMEILOF Do not generate Na+ current; slow down recovery from fast inactivation.Bechi G.2012
5c.680T>Gp.Ile227Ser(I227S)DIS4(V-sensor)SMEI LOF No measurable sodium current.Ohmori I.2006
6c.787C>Gp.Leu263Val(L263V)DIS5(pore region)FHM+EPGOF 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
7c.902A>Gp.Asn301Ser(N301S)DIS5-S6(pore region)ArtificialLOFNo measurable sodium current Chen YJ.2014
8c.1178G>Ap.Arg393His(R393H)DIS5-S6(pore region)SMEI LOF No measurable sodium current.Ohmori I.2006
9c.1276T>Ap.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
10c.2134C>Tp.Arg712X(R712X)DI-DII (D-linkers)SMEILOFExtremely small Na+ currents, generate non-functional channel.Sugawara T.2003
11c.2422A>Tp.Thr808Ser(T808S)DIIS2 ICEGTC IE Increased current density, delayed both onset and recovery from slow inactivation.Rhodes TH.2005
12c.2575C>Tp.Arg859Cys(R859C)DIIS4(V-sensor)GEFS+ fDE Hypoexcitable (positive) shift of activation, slower recovery from slow inactivation, lower levels of current.Barela AJ.2006
13c.2576G>Ap.Arg859His(R859H)DIIS4(V-sensor)PEFS+ fG-LOFIncreased 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
14c.2589+3A>Tp.Val806_Leu863del(V806_L863del) DIIS4(V-sensor) SMEI LOF No measurable sodium current. Liu Y.2013
15c.2593C>Gp.Arg865Gly(R865G)DIIS4(V-sensor)SMEIG-LOFA 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
16c.2624C>Tp.Thr875Met(T875M)DIIS4(V-sensor)PEFS+ fG-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
17c.2705T>Gp.Phe902Cys(F902C)DIIS5(pore region)SMEILOF No measurable sodium current.Rhodes TH.2004
18c.2817C>Gp.His939Gln(H939Q)DIIS5-S6(pore region)SMEI LOF No measurable sodium current.Ohmori I.2006
19c.2836C>Tp.Arg946Cys(R946C)DIIS5-S6(pore region)SMEI LOF No measurable sodium current.Volkers L.2011
20c.2837G>Ap.Arg946His(R946H)DIIS5-S6(pore region)PEFS+ LOF No measurable sodium current .Liao WP.2010
21c.2875T>Cp.Cys959Arg(C959R)DIIS5-S6(pore region)SMEI LOF No measurable sodium current.Ohmori I.2006
22c.2935G>Ap.Gly979Arg(G979R)DIIS6(pore region)ICEGTC LOF No measurable sodium current.Rhodes TH.2005; Sugawara T.2003
23c.2948T>Cp.Val983Ala(V983A)DIIS6(pore region)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
24c.2954A>Tp.Asn985Ile(N985I)DIIS6(pore region)SMEI LOF Extremely small Na+ currents, generate non-functional channel.Sugawara T. 2003
25c.2956C>Tp.Leu986Phe(L986F)DIIS6(pore region)SMEI LOF No measurable sodium current.Lossin C.2003
26c.3032A>Tp.Asn1011Ile(N1011I)DII-DIII (D-linkers)ICEGTC pLOF Reduced current density, negative shift of inactivation.Rhodes TH.2005
27c.3521C>Gp.Thr1174Ser (T1174S)DII-DIII (D-linkers)PEFS+ fG-LOFIncrease of persistent current; positive shift of the activation curve and deceleration of recovery from fast inactivation, consistent with loss of function.Cestèle S.2013
28c.3610T>Cp.Trp1204Arg(W1204R)DII-DIII (D-linkers)GEFS+ fGOF 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
29c.3733C>Tp.Arg1245X(R1245X) (Arg1234X,R1234X)DIII S1-S2SMEILOFDo not generate Na+ current; slow down recovery from fast inactivation.Bechi G.2012
30c.3867_3869delCTTp.Phe1289del(F1289del)DIIIS3SMEBLOFNo measurable sodium current.Ohmori I.2006
31c.4057G>Cp.Val1353Leu(V1353L)DIIIS5(pore region)PEFS+ fLOF No measurable sodium current.Lossin C.2003
32c.4219C>Tp.Arg1407X (R1396X)DIIIS5-S6(pore region)SMEILOFExtremely small Na+ currents, generate non-functional channel.Sugawara T.2003
33c.4465C>Ap.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
34c.4723C>Tp.Arg1575Cys(R1575C)DIVS2Rasmussen encephalitis fGOF Exhibited increased channel availability and an increased persistent sodium current in comparison to the wild-type.Ohmori I.2008
35c.4831G>Tp.Val1611Phe(V1611F)DIVS3GEFS+ fGOF Small persistent current, hyperexcitable shift of window current (negative shift in both activation and inactivation curve).Rhodes TH.2005
36c.4894C>Tp.Pro1632Ser(P1632S)DIVS3-S4(V-sensor)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
37c.4942C>Tp.Arg1648Cys(R1648C)DIVS4(V-sensor)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
38c.4943G>Ap.Arg1648His(R1648H)DIVS4(V-sensor)GEFS+ fG-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
39c.4946T>Ap.Leu1649Gln(L1649Q) DIVS4 FHM LOFFailed to generate measurable whole-cell current. Kahlig KM.2008
40c.4968C>Gp.Ile1656Met(I1656M)DIVS4(V-sensor)GEFS+ fDE Hypoexcitable (positive) shift of activation and negative shift of inactivation.Lossin C. 2003
41c.4969C>Tp.Arg1657Cys(R1657C)DIVS4(V-sensor)SMEI fG-LOF Reduced current density and hypoexcitable (positive) shift of activation. Accelerated recovery from fast and slow inactivation.Lossin C. 2003
42c.4982T>Cp.Phe1661Ser(F1661S)DIVS4-S5(V-sensor)SMEI G-LOF Big persistent current. Reduced current density, impaired recovery from slow inactivation.Rhodes TH.2004
43c.5020G>Cp.Gly1674Arg(G1674R)DIVS5(pore region)SMEI LOF No measurable sodium current.Rhodes TH.2004
44c.5054C>Tp.Ala1685Val(A1685V)DIVS5(pore region)PEFS+ fLOF No measurable sodium current.Sugiura Y.2012
45c.5054C>Ap.Ala1685Asp(A1685D)DIVS5(pore region)SMEILOF The mutant channel with and without b1 subunit did not conduct any sodium currents.Sugiura Y.2012
46c.5126C>Tp.Thr1709Ile(T1709I)DIVS5-S6(pore region)ICEGTC fLOF No measurable sodium current.Rhodes TH.2005
47c.5246G>Ap.Gly1749Glu(G1749E)DIVS5-S6(pore region)SMEI pLOF Reduced current density, faster onset of slow inactivation.Rhodes TH.2004
48c.5295T>Ap.Phe1765Leu(F1765L)DIVS6(pore region)PEFS+ LOF No measurable sodium current.Liao WP.2010
49c.5422T>Cp.Phe1808Leu(F1808L)C-terminalICEGTC 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
50c.5492T>Cp.Phe1831Ser(F1831S)C-terminalSMEI pLOF Apparent reduction of peak current.Sugawara T. 2003
51c.5555T>Cp.Met1852Thr(M1852T)C-terminalSMEI fpLOF Reduced current density that could be partially rescued, with trafficking defect involved.Rusconi R.2007
52c.5596G>Tp.Asp1866Tyr(D1866Y)C-Terminal GEFS+ fGOF Positive shift of fast inactivation due to reduced association with β1 subunit, persistent current.Spampanato J.2004
53c.5674C>Tp.Arg1892X (R1881X)C-Terminal SMEIpLOF Showed a drastic attenuation of the peak Na+ current, small yet detectable sodium currents.Sugawara T. 2003
54c.5726C>Tp.Thr1909Ile(T1909I)C-terminalSMEI G-LOF Reduced current density. Small persistent current.Ohmori I.2006
55c.5779A>Gp.Arg1927Gly(R1927G) (Arg1916Gly,R1916G)C-terminalGEFS+ fpLOF Loss of function caused by folding defects that can be rescued by molecular interactions with associated proteins and drugs.Rusconi R.2009