SCN5A Variant D1790G

Summary of observed carriers, functional annotations, and structural context for SCN5A D1790G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

80%

40/55 effective observations

Estimated BrS1 penetrance

4%

2/55 effective observations

Total carriers

45

1 BrS1 · 38 LQT3 · 6 unaffected

D1790G has not been reported 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 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 (%)
-6.47 1 -4.39 0.992 2 56

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
10627139 1998 26 23 0 0
10973849 2000 1 1 0 0
16414944 2005 1 1 0 0
19140927 2009 1 1 0 0
20102920 2010 35 35 0 0
22360817 2012 2 2 0 0
26304620 2015 2 0 1 0
26669661 2016 14 12 0 0
27566755 2016 30 30 0 0
28339995 2017 85 85 0 0
27733495 2016 8 8 0 0
30059973 2018 7 7 0 0
Literature, cohort, and gnomAD – 45 6 38 1 –
Variant features alone – 15 12 2 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)
28087622 2017 HEK 81 5.12 -14.8 121
9686753 1998 HEK 83 0 -16.3
11150514 2000 HEK 100 5.36 -14.64 2000
10627139 1998
10758053 2000
10973849 2000
12814325 2003
16414944 2005
19140927 2009
20102920 2010
22360817 2012
26304620 2015
26669661 2016
29017927 2017
12401812 2003
27566755 2016
28339995 2017
10952963 2000 HEK -15.6
25370050 2014 HEK 3.9 -13.5
27733495 2016 tsA201
10920073 2000 HEK 7 -15
30059973 2018

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 D1790G.
Neighbour residue Distance (Å) Observed variants
1850 15 C1850S, C1850S,
1855 15
1785 9
1794 8
1856 14
1778 12
1853 14 I1853V,
1795 10 Y1795N, Y1795H, p.Y1795_E1796insD, Y1795C,
1818 13
1652 15 M1652T, M1652R,
1777 15 V1777M, V1777L, V1777L,
1824 7 P1824A,
1820 12 A1820T, A1820V,
1504 11 K1504E,
1641 9
1501 11 p.L1501_K1505del, L1501V,
1860 14 c.5577_5578dupAA,
1857 12
1862 13
1639 13 G1639A,
1779 14 T1779M,
1493 14 p.K1493del, K1493X, K1493R,
1858 10
1865 14
1787 4 S1787N,
1786 5 c.5356_5357delCT, L1786Q, L1786R,
1648 11
1861 10 V1861I, V1861F
1649 14 A1649V,
1864 14
1821 9
1644 10 R1644C, R1644H, R1644L,
1640 14
1798 14 W1798X,
1826 11 R1826C, R1826H,
1496 13
1854 11
1825 7 L1825P,
1797 11 I1797V,
1793 6 M1793K,
1781 10 E1781G, E1781D, E1781D,
1789 4
1817 13
1645 10 T1645M,
1784 13 E1784K, E1784X,
1827 14
1498 14 M1498V, M1498T, M1498R,
1796 10
1780 15 E1780G,
1788 7 c.5361_5364delTGAG,
1638 11 R1638X, R1638Q,
1500 9 p.K1500del,
1791 5
1637 14
1792 7 D1792N, D1792Y, D1792V,
1823 9 E1823K, p.E1823HfsX10,
1502 15 G1502S, G1502A,
1783 12
1642 13 G1642E,
1497 11
1790 0 D1790N, D1790G, p.D1790del,
1647 15
1503 14 S1503Y,
1822 7 c.5464_5467delTCTG, c.5464-5467delTCTG,
1646 15
1782 10