SCN5A Variant c.3288+2delT

Summary of observed carriers, functional annotations, and structural context for SCN5A c.3288+2delT. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

31%

3/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.3288+2delT has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
NA NA NA None 29 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
21273195 2011 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 13 0 2 – –

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)
21273195 2011

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 c.3288+2delT.
Neighbour residue Distance (Å) Observed variants
1082 15 V1082A,
1083 14 S1083C,
1084 14 G1084S, G1084R, G1084D,
1085 13
1086 13
1087 12
1088 11 A1088T, A1088V,
1089 11
1090 10 P1090Q, P1090L,
1091 9 D1091A, D1091Y,
1092 8
1093 8
1094 7
1095 5 W1095X, W1095C, W1095C,
1096 4 S1096C, S1096G,
1097 0 Q1097H, c.3288+2delT, Q1097H,
1098 4 V1098L, V1098L, V1098M,
1099 5
1100 7 A1100T, A1100V,
1101 8
1102 8 A1102T,
1103 9 S1103F, S1103Y,
1104 10
1105 11 E1105V, E1105X,
1106 11 A1106T,
1107 12 p.E1107RfsX24, E1107X, E1107K,
1108 13
1109 13 S1109G,
1110 14
1111 14
1112 15 Q1112X,