SCN5A Variant D1114E

Summary of observed carriers, functional annotations, and structural context for SCN5A D1114E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

46%

6/20 effective observations

Estimated BrS1 penetrance

2%

0/20 effective observations

Total carriers

10

0 BrS1 · 6 LQT3 · 4 unaffected

D1114E is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Mild_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 (%)
-0.71 0 2.89 0.27 5 18

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
26669661 2016 9 6 0 0
27566755 2016 15 15 0 0
Literature, cohort, and gnomAD – 10 4 6 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)
26669661 2016
27566755 2016

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 D1114E.
Neighbour residue Distance (Å) Observed variants
1099 15
1100 14 A1100T, A1100V,
1101 14
1102 13 A1102T,
1103 13 S1103F, S1103Y,
1104 12
1105 11 E1105V, E1105X,
1106 11 A1106T,
1107 10 E1107X, E1107K, p.E1107RfsX24,
1108 9
1109 8 S1109G,
1110 8
1111 7
1112 5 Q1112X,
1113 4 A1113V, A1113T,
1114 0 D1114E, D1114E, D1114N,
1115 4 W1115R, W1115R, W1115X,
1116 5 R1116Q, R1116W,
1117 7
1118 8 Q1118X,
1119 8
1120 9
1121 10 A1121V,
1122 11
1123 11
1124 12
1125 13 A1125T, A1125G, A1125V,
1126 13
1127 14
1128 14 C1128X,
1129 15 G1129S,