SCN5A Variant A1113V

Summary of observed carriers, functional annotations, and structural context for SCN5A A1113V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/17 effective observations

Estimated BrS1 penetrance

10%

1/17 effective observations

Total carriers

7

1 BrS1 · 0 LQT3 · 6 unaffected

A1113V is present in 6 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 (%)
0.45 0.136 -0.66 0.521 6 14

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 – 7 6 0 1 –
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)
20129283 2010
24573164 2014 HEK 100 -0.78

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 A1113V.
Neighbour residue Distance (Å) Observed variants
1098 15 V1098L, V1098M, V1098L,
1099 14
1100 14 A1100T, A1100V,
1101 13
1102 13 A1102T,
1103 12 S1103F, S1103Y,
1104 11
1105 11 E1105V, E1105X,
1106 10 A1106T,
1107 9 E1107X, E1107K, p.E1107RfsX24,
1108 8
1109 8 S1109G,
1110 7
1111 5
1112 4 Q1112X,
1113 0 A1113V, A1113T,
1114 4 D1114E, D1114E, D1114N,
1115 5 W1115R, W1115R, W1115X,
1116 7 R1116Q, R1116W,
1117 8
1118 8 Q1118X,
1119 9
1120 10
1121 11 A1121V,
1122 11
1123 12
1124 13
1125 13 A1125T, A1125G, A1125V,
1126 14
1127 14
1128 15 C1128X,