SCN5A Variant E1489D
Summary of observed carriers, functional annotations, and structural context for SCN5A E1489D. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
56%
3/12 effective observations
Estimated BrS1 penetrance
5%
0/12 effective observations
Total carriers
2
0 BrS1 · 1 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 2 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -2.76 | 0.286 | 2.04 | 0.798 | 2 | 78 |
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 | – | 2 | 1 | 1 | 0 | – | |
| Variant features alone | – | 15 | 13 | 2 | 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 |
|---|---|---|
| 414 | 15 | M414V, |
| 1785 | 12 | |
| 1778 | 12 | |
| 1773 | 12 | |
| 943 | 14 | S943N, |
| 1486 | 9 | F1486L, p.F1486del, F1486L, F1486L, |
| 1777 | 9 | V1777M, V1777L, V1777L, |
| 1485 | 11 | |
| 1487 | 6 | M1487L, M1487L, M1487K, |
| 1492 | 6 | |
| 417 | 13 | |
| 1477 | 12 | K1477N, K1477N, |
| 1491 | 8 | Q1491H, Q1491H, |
| 1471 | 14 | |
| 1779 | 12 | T1779M, |
| 1493 | 6 | p.K1493del, K1493X, K1493R, |
| 1478 | 9 | K1478E, |
| 1776 | 10 | |
| 1495 | 11 | Y1495S, |
| 1774 | 14 | N1774D, c.5321_5324dupACTT, |
| 1479 | 15 | |
| 1496 | 10 | |
| 1474 | 10 | |
| 1481 | 12 | G1481R, G1481R, G1481E, G1481V, |
| 1781 | 10 | E1781G, E1781D, E1781D, |
| 1784 | 11 | E1784K, E1784X |
| 1488 | 4 | T1488R, |
| 1780 | 8 | E1780G, |
| 1482 | 11 | |
| 1868 | 14 | |
| 1783 | 11 | |
| 1775 | 15 | F1775V, p.F1775LfsX15, |
| 1484 | 10 | |
| 421 | 13 | |
| 1497 | 14 | |
| 1490 | 6 | |
| 1475 | 12 | p.Q1475NfsX6, Q1475L, |
| 1483 | 10 | Q1483H, Q1483H, |
| 1494 | 12 | |
| 1489 | 0 | E1489D, E1489D, |
| 1782 | 13 |