SCN5A Variant V1098L

Summary of observed carriers, functional annotations, and structural context for SCN5A V1098L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

2/50 effective observations

Estimated BrS1 penetrance

2%

1/50 effective observations

Total carriers

40

0 BrS1 · 2 LQT3 · 38 unaffected

V1098L is present in 37 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 (%)
0.35 0.021 1.31 0.387 8 3

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
20541041 2010 2 2 0 0
27707468 2016 1 0 0 1 SUNDS
24529773 2014 1 0 0 1 SUNDS
20129283 2010 1 0 0 0
Literature, cohort, and gnomAD – 40 38 2 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)
20541041 2010
27707468 2016
24529773 2014
20129283 2010

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 V1098L.
Neighbour residue Distance (Å) Observed variants
1083 15 S1083C,
1084 14 G1084S, G1084R, G1084D,
1085 14
1086 13
1087 13
1088 12 A1088T, A1088V,
1089 11
1090 11 P1090Q, P1090L,
1091 10 D1091A, D1091Y,
1092 9
1093 8
1094 8
1095 7 W1095C, W1095X, W1095C,
1096 5 S1096C, S1096G,
1097 4 c.3288+2delT, Q1097H, Q1097H,
1098 0 V1098L, V1098L, V1098M,
1099 4
1100 5 A1100V, A1100T
1101 7
1102 8 A1102T,
1103 8 S1103Y, S1103F,
1104 9
1105 10 E1105X, E1105V,
1106 11 A1106T,
1107 11 E1107K, E1107X, p.E1107RfsX24,
1108 12
1109 13 S1109G,
1110 13
1111 14
1112 14 Q1112X,
1113 15 A1113T, A1113V,