SCN5A Variant c.3940_3941delCT
Summary of observed carriers, functional annotations, and structural context for SCN5A c.3940_3941delCT. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/11 effective observations
Estimated BrS1 penetrance
52%
5/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 4 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 | 69 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| 19026623 | 2009 | 1 | 0 | 1 | 0 | ||
| 24687331 | 2014 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 0 | 4 | – | – |
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.
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 |
|---|---|---|
| 1328 | 13 | V1328M, |
| 1659 | 8 | |
| 1271 | 11 | W1271C, W1271C, |
| 1315 | 5 | |
| 1274 | 14 | |
| 1216 | 11 | L1216V, |
| 1314 | 0 | c.3940_3941delCT, |
| 1320 | 5 | M1320I, M1320I, M1320I, |
| 1213 | 15 | |
| 1666 | 7 | |
| 1656 | 12 | |
| 1309 | 12 | R1309C, R1309H, |
| 1669 | 12 | |
| 1668 | 14 | M1668T, |
| 1219 | 14 | S1219N, |
| 1660 | 10 | I1660V, I1660S, |
| 1313 | 5 | |
| 1310 | 7 | |
| 1316 | 8 | R1316Q, R1316L, |
| 1766 | 14 | M1766L, M1766V, M1766L, M1766T |
| 1319 | 9 | G1319V, |
| 1665 | 10 | |
| 1663 | 7 | |
| 1657 | 14 | |
| 1662 | 6 | |
| 1324 | 8 | |
| 1317 | 6 | F1317C, |
| 1327 | 12 | |
| 1307 | 12 | |
| 1318 | 10 | |
| 1321 | 9 | R1321K, |
| 1323 | 9 | V1323G, |
| 1215 | 12 | I1215V, |
| 1212 | 10 | p.I1212del, |
| 1322 | 11 | c.3963+2T>C, c.3963+4A>G, |
| 1211 | 14 | |
| 1312 | 7 | |
| 1326 | 13 | A1326S, |
| 1763 | 13 | V1763M, V1763L, V1763L, |
| 1311 | 6 | L1311P, |
| 1308 | 11 | L1308F, |
| 1670 | 12 | |
| 1661 | 10 | G1661R, G1661R, G1661E, |
| 1209 | 13 | T1209R, |
| 1655 | 13 | |
| 1325 | 12 | N1325S, |
| 1208 | 14 | E1208K, E1208X, |
| 1667 | 11 | V1667I, |
| 1664 | 11 | |
| 1658 | 13 |