SCN5A Variant S1219N
Summary of observed carriers, functional annotations, and structural context for SCN5A S1219N. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/11 effective observations
Estimated BrS1 penetrance
45%
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 (%) |
|---|---|---|---|---|---|
| -2.93 | 0.991 | -3.68 | 0.855 | 57 | 8 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 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) |
|---|---|---|---|---|---|---|
| 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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 1245 | 13 | M1245I, M1245I, M1245I, |
| 1218 | 4 | S1218T, S1218I, |
| 1304 | 10 | T1304M, |
| 1217 | 6 | |
| 1243 | 12 | D1243N, |
| 1216 | 5 | L1216V, |
| 1698 | 15 | A1698T, |
| 1314 | 14 | c.3940_3941delCT, |
| 1220 | 4 | G1220E, |
| 1673 | 9 | |
| 1675 | 15 | |
| 1213 | 10 | |
| 1210 | 14 | F1210S, |
| 1241 | 15 | |
| 1309 | 10 | R1309C, R1309H, |
| 1226 | 13 | |
| 1669 | 7 | |
| 1671 | 14 | |
| 1221 | 5 | A1221V, |
| 1242 | 11 | |
| 1668 | 14 | M1668T, |
| 1676 | 13 | M1676T, M1676I, M1676I, M1676I, |
| 1219 | 0 | S1219N, |
| 1672 | 11 | S1672Y, |
| 1313 | 13 | |
| 1239 | 10 | L1239P, |
| 1310 | 8 | |
| 1306 | 8 | R1306S, R1306H, |
| 1665 | 11 | |
| 1305 | 12 | |
| 1246 | 10 | |
| 1235 | 13 | |
| 1282 | 15 | S1282A, |
| 1662 | 15 | |
| 1247 | 15 | T1247I, |
| 1701 | 14 | M1701I, M1701I, M1701I |
| 1307 | 7 | |
| 1223 | 7 | c.3667delG, |
| 1697 | 11 | |
| 1275 | 15 | D1275N, |
| 1222 | 5 | p.L1222LfsX7, L1222R, |
| 1674 | 14 | F1674V, |
| 1215 | 7 | I1215V, |
| 1301 | 13 | |
| 1214 | 10 | M1214T, |
| 1212 | 11 | p.I1212del, |
| 1696 | 15 | |
| 1211 | 13 | |
| 1700 | 15 | |
| 1311 | 12 | L1311P, |
| 1677 | 15 | |
| 1308 | 10 | L1308F, |
| 1250 | 13 | |
| 1224 | 9 | |
| 1670 | 10 | |
| 1240 | 14 | E1240Q, |
| 1225 | 10 | E1225K, G1225K, |
| 1278 | 13 | I1278N, |
| 1238 | 14 | |
| 1249 | 14 | V1249D, |
| 1667 | 14 | V1667I, |
| 1303 | 10 | R1303W, R1303Q, |
| 1666 | 10 |