SCN5A Variant E1781A

Summary of observed carriers, functional annotations, and structural context for SCN5A E1781A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

52%

2/10 effective observations

Estimated BrS1 penetrance

15%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

E1781A has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
NA NA NA 0.898 12 71

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
Literature, cohort, and gnomAD – 0 0 0 0 –
Variant features alone – 15 12 2 1 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 E1781A.
Neighbour residue Distance (Å) Observed variants
414 13 M414V,
1785 5
1778 5
1773 12
1653 15
1652 10 M1652T, M1652R,
1824 13 P1824A,
1777 5 V1777M, V1777L, V1777L,
1650 14 L1650F,
1492 9
1504 15 K1504E,
1641 13
1477 14 K1477N, K1477N,
1491 12 Q1491H, Q1491H,
1501 13 L1501V, p.L1501_K1505del,
1862 12
1779 7 T1779M,
1493 6 K1493X, K1493R, p.K1493del,
1858 13
1865 13
1478 15 K1478E,
1776 8
1787 6 S1787N,
1786 7 L1786R, L1786Q, c.5356_5357delCT,
1648 10
1861 13 V1861I, V1861F,
1495 11 Y1495S,
1649 11 A1649V,
1774 10 N1774D, c.5321_5324dupACTT,
1644 14 R1644H, R1644C, R1644L,
1496 7
1474 15
1481 14 G1481R, G1481V, G1481E, G1481R,
1825 15 L1825P,
1781 0 E1781D, E1781G, E1781D,
1789 11
1772 15 L1772V,
1499 12
1645 10 T1645M,
1488 14 T1488R,
1784 8 E1784K, E1784X,
1498 12 M1498T, M1498R, M1498V,
1780 6 E1780G,
1788 9 c.5361_5364delTGAG,
1651 15
1500 9 p.K1500del,
1791 10
1482 15
1792 14 D1792N, D1792V, D1792Y,
1783 7
1775 10 F1775V, p.F1775LfsX15,
1642 13 G1642E,
1497 8
1490 11
1790 10 p.D1790del, D1790N, D1790G,
1494 11
1647 15
1503 15 S1503Y,
1646 13
1489 10 E1489D, E1489D,
1782 6