SCN5A Variant A1148T

Summary of observed carriers, functional annotations, and structural context for SCN5A A1148T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/17 effective observations

Estimated BrS1 penetrance

3%

0/17 effective observations

Total carriers

7

0 BrS1 · 0 LQT3 · 7 unaffected

A1148T is present in 6 alleles in gnomAD. This residue resides in a Non_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 (%)
-1.47 0.075 -0.03 0.45 0 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
15996170 2005 1 0 0 0
Literature, cohort, and gnomAD – 7 7 0 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)
15996170 2005

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 A1148T.
Neighbour residue Distance (Å) Observed variants
1133 15
1134 14 D1134N, D1134E, D1134E,
1135 14 S1135I,
1136 13 C1136Y,
1137 13
1138 12
1139 11
1140 11 S1140T,
1141 10
1142 9
1143 8
1144 8
1145 7
1146 5
1147 4 T1147I, T1147N, T1147S, T1147S,
1148 0 A1148S, A1148T,
1149 4
1150 5
1151 7
1152 8 E1152X,
1153 8 Q1153H, Q1153H,
1154 9 I1154N,
1155 10 P1155S,
1156 11 D1156G,
1157 11
1158 12 G1158S,
1159 13
1160 13
1161 14 c.3480delT,
1162 14
1163 15 D1163G, D1163E, D1163Y, D1163E,