SCN5A Variant S1140T

Summary of observed carriers, functional annotations, and structural context for SCN5A S1140T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/11 effective observations

Estimated BrS1 penetrance

52%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

S1140T has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-2.51 1 0.01 0.854 83 0

PROVEAN scores below -2 suggest deleterious impact. REVEL scores above 0.5–0.75 are often interpreted as likely pathogenic. PolyPhen-2 scores above 0.85 are typically pathogenic. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 11 0 4 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
20129283 2010
24573164 2014 HEK 100 -3.05

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near S1140T.
Neighbour residue Distance (Å) Observed variants
1125 15 A1125V, A1125G, A1125T,
1126 14
1127 14
1128 13 C1128X,
1129 13 G1129S,
1130 12 E1130K,
1131 11 T1131I, T1131S, T1131S, c.3391-1G>A, c.3390-1G>A,
1132 11 P1132S,
1133 10
1134 9 D1134N, D1134E, D1134E,
1135 8 S1135I,
1136 8 C1136Y,
1137 7
1138 5
1139 4
1140 0 S1140T,
1141 4
1142 5
1143 7
1144 8
1145 8
1146 9
1147 10 T1147I, T1147N, T1147S, T1147S,
1148 11 A1148S, A1148T,
1149 11
1150 12
1151 13
1152 13 E1152X,
1153 14 Q1153H, Q1153H,
1154 14 I1154N,
1155 15 P1155S,