SCN5A Variant D1166N
Summary of observed carriers, functional annotations, and structural context for SCN5A D1166N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
50%
2/11 effective observations
Estimated BrS1 penetrance
2%
0/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -1.83 | 0.07 | 0.83 | 0.329 | 1 | 50 |
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 |
|---|---|---|---|---|---|---|---|
| 19716085 | 2009 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 14 | 1 | 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 19716085 | 2009 |
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 |
|---|---|---|
| 1151 | 15 | |
| 1152 | 14 | E1152X, |
| 1153 | 14 | Q1153H, Q1153H, |
| 1154 | 13 | I1154N, |
| 1155 | 13 | P1155S, |
| 1156 | 12 | D1156G, |
| 1157 | 11 | |
| 1158 | 11 | G1158S, |
| 1159 | 10 | |
| 1160 | 9 | |
| 1161 | 8 | c.3480delT, |
| 1162 | 8 | |
| 1163 | 7 | D1163E, D1163Y, D1163E, D1163G, |
| 1164 | 5 | P1164T, |
| 1165 | 4 | E1165D, E1165D, p.E1165RfsX6, E1165Q, |
| 1166 | 0 | D1166N, |
| 1167 | 4 | C1167Y, |
| 1168 | 5 | F1168L, F1168L, F1168L, |
| 1169 | 7 | T1169I, |
| 1170 | 8 | |
| 1171 | 8 | c.3511+10C>T, |
| 1172 | 9 | |
| 1173 | 10 | V1173D, |
| 1174 | 11 | R1174G, R1174W, |
| 1175 | 11 | R1175H, |
| 1176 | 12 | |
| 1177 | 13 | P1177L, |
| 1178 | 13 | C1178Y, |
| 1179 | 14 | |
| 1180 | 14 | A1180V, |
| 1181 | 15 | V1181L, V1181L, V1181A, V1181M, |