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

E1489D is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational 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

Observed carriers by publication or cohort.
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.

Published electrophysiology measurements.
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.

Previously observed variants near E1489D.
Neighbour residue Distance (Å) Observed variants
414 15 M414V,
1785 12
1778 12
1773 12
943 14 S943N,
1486 9 F1486L, F1486L, p.F1486del, F1486L,
1777 9 V1777L, V1777L, V1777M,
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 K1493R, K1493X, p.K1493del,
1478 9 K1478E,
1776 10
1495 11 Y1495S,
1774 14 N1774D, c.5321_5324dupACTT,
1479 15
1496 10
1474 10
1481 12 G1481V, G1481R, G1481E, G1481R,
1781 10 E1781D, E1781D, E1781G,
1784 11 E1784X, E1784K,
1488 4 T1488R,
1780 8 E1780G,
1482 11
1868 14
1783 11
1775 15 p.F1775LfsX15, F1775V,
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