SCN5A Variant A1100V

Summary of observed carriers, functional annotations, and structural context for SCN5A A1100V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

1/26 effective observations

Estimated BrS1 penetrance

4%

1/26 effective observations

Total carriers

16

0 BrS1 · 1 LQT3 · 15 unaffected

A1100V is present in 15 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 1 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 (%)
-0.41 0.05 -1.25 0.621 3 2

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
24631775 2014 1 0 0 1 SIDS
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 16 15 1 0 –
Variant features alone – 15 14 0 1 – –

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)
19716085 2009
24631775 2014

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 A1100V.
Neighbour residue Distance (Å) Observed variants
1085 15
1086 14
1087 14
1088 13 A1088V, A1088T,
1089 13
1090 12 P1090L, P1090Q,
1091 11 D1091A, D1091Y,
1092 11
1093 10
1094 9
1095 8 W1095C, W1095C, W1095X,
1096 8 S1096C, S1096G,
1097 7 c.3288+2delT, Q1097H, Q1097H,
1098 5 V1098M, V1098L, V1098L,
1099 4
1100 0 A1100T, A1100V,
1101 4
1102 5 A1102T,
1103 7 S1103Y, S1103F,
1104 8
1105 8 E1105V, E1105X,
1106 9 A1106T,
1107 10 p.E1107RfsX24, E1107K, E1107X,
1108 11
1109 11 S1109G,
1110 12
1111 13
1112 13 Q1112X,
1113 14 A1113T, A1113V,
1114 14 D1114E, D1114E, D1114N,
1115 15 W1115X, W1115R, W1115R,