SCN5A Variant c.3391-1G>A
Summary of observed carriers, functional annotations, and structural context for SCN5A c.3391-1G>A. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/11 effective observations
Estimated BrS1 penetrance
37%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 41 | 0 |
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
| Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
|---|---|---|---|---|---|---|---|
| 27232914 | 2016 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 27232914 | 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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 1116 | 15 | R1116Q, R1116W, |
| 1117 | 14 | |
| 1118 | 14 | Q1118X, |
| 1119 | 13 | |
| 1120 | 13 | |
| 1121 | 12 | A1121V, |
| 1122 | 11 | |
| 1123 | 11 | |
| 1124 | 10 | |
| 1125 | 9 | A1125T, A1125G, A1125V, |
| 1126 | 8 | |
| 1127 | 8 | |
| 1128 | 7 | C1128X, |
| 1129 | 5 | G1129S, |
| 1130 | 4 | E1130K, |
| 1131 | 0 | c.3390-1G>A, T1131I, c.3391-1G>A, T1131S, T1131S, |
| 1132 | 4 | P1132S, |
| 1133 | 5 | |
| 1134 | 7 | D1134N, D1134E, D1134E, |
| 1135 | 8 | S1135I |
| 1136 | 8 | C1136Y, |
| 1137 | 9 | |
| 1138 | 10 | |
| 1139 | 11 | |
| 1140 | 11 | S1140T, |
| 1141 | 12 | |
| 1142 | 13 | |
| 1143 | 13 | |
| 1144 | 14 | |
| 1145 | 14 | |
| 1146 | 15 |