SCN5A Variant S1135I

Summary of observed carriers, functional annotations, and structural context for SCN5A S1135I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

13%

2/22 effective observations

Estimated BrS1 penetrance

4%

0/22 effective observations

Total carriers

12

0 BrS1 · 2 LQT3 · 10 unaffected

S1135I is present in 10 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-3.2 0.784 -1.53 0.635 5 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
24667783 2015 1 1 0 0
26071830 2015 1 1 0 0
Literature, cohort, and gnomAD – 12 10 2 0 –
Variant features alone – 15 15 0 0 – –

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)
24667783 2015
26071830 2015

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 S1135I.
Neighbour residue Distance (Å) Observed variants
1130 8 E1130K,
1131 8 c.3390-1G>A, T1131I, c.3391-1G>A, T1131S, T1131S,
1132 7 P1132S,
1133 5
1134 4 D1134N, D1134E, D1134E,
1135 0 S1135I
1136 4 C1136Y,
1137 5
1138 7
1139 8
1140 8 S1140T,
1141 9
1142 10
1143 11
1144 11
1145 12
1146 13
1147 13 T1147I, T1147N, T1147S, T1147S,
1148 14 A1148S, A1148T,
1149 14
1150 15
1120 15
1121 14 A1121V,
1122 14
1123 13
1124 13
1125 12 A1125T, A1125G, A1125V,
1126 11
1127 11
1128 10 C1128X,
1129 9 G1129S,