SCN5A Variant S1787N

Summary of observed carriers, functional annotations, and structural context for SCN5A S1787N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

3/250 effective observations

Estimated BrS1 penetrance

1%

2/250 effective observations

Total carriers

240

1 BrS1 · 2 LQT3 · 237 unaffected

S1787N is present in 234 alleles 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 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-2.32 0.976 0.16 0.86 12 41

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
10973849 2000 1 1 0 0
16414944 2005 1 1 0 0
23631430 2013 1 1 0 0
23503384 2013 1 0 1 0
28069705 2017 1 0 0 1 ARVD
20129283 2010 3 0 0 0
Literature, cohort, and gnomAD – 240 237 2 1 –
Variant features alone – 15 13 1 1 – –

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)
25923670 2015 HEK 95 1 0 210
10973849 2000
15851227 2004
15898185 2004
16414944 2005
23631430 2013
29017927 2017
23503384 2013
28069705 2017
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.

Previously observed variants near S1787N.
Neighbour residue Distance (Å) Observed variants
1785 7
1794 11
1643 14 I1643L,
1778 8
1795 13 Y1795N, Y1795H, p.Y1795_E1796insD, Y1795C,
1652 11 M1652T, M1652R,
1777 11 V1777M, V1777L, V1777L,
1824 10 P1824A,
1650 15 L1650F,
1492 14
1504 12 K1504E,
1641 9
1501 12 p.L1501_K1505del, L1501V,
1857 15
1862 13
1639 14 G1639A,
1779 10 T1779M,
1493 11 p.K1493del, K1493X, K1493R,
1858 11
1865 14
1776 13
1787 0 S1787N,
1786 4 c.5356_5357delCT, L1786Q, L1786R,
1648 8
1861 11 V1861I, V1861F
1495 15 Y1495S,
1649 11 A1649V,
1774 13 N1774D, c.5321_5324dupACTT,
1821 13
1644 10 R1644C, R1644H, R1644L,
1640 14
1826 14 R1826C, R1826H,
1496 10
1854 13
1825 10 L1825P,
1797 15 I1797V,
1793 10 M1793K,
1781 6 E1781G, E1781D, E1781D,
1789 5
1499 14
1645 8 T1645M,
1784 11 E1784K, E1784X,
1498 13 M1498V, M1498T, M1498R,
1796 13
1780 11 E1780G,
1788 5 c.5361_5364delTGAG,
1638 12 R1638X, R1638Q,
1651 13
1500 8 p.K1500del,
1791 6
1637 14
1792 8 D1792N, D1792Y, D1792V,
1823 12 E1823K, p.E1823HfsX10,
1502 15 G1502S, G1502A,
1783 10
1775 13 F1775V, p.F1775LfsX15,
1642 12 G1642E,
1497 9
1790 4 D1790N, D1790G, p.D1790del,
1494 14
1647 13
1503 13 S1503Y,
1822 11 c.5464_5467delTCTG, c.5464-5467delTCTG,
1646 12
1782 7