SCN5A Variant C1850S

Summary of observed carriers, functional annotations, and structural context for SCN5A C1850S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

14%

0/11 effective observations

Estimated BrS1 penetrance

42%

4/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

C1850S has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-9.23 0.947 -2.23 0.957 47 12

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
18252757 2008 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 12 0 3 – –

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)
18252757 2008 HEK 38 1.4 -11.6

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 C1850S.
Neighbour residue Distance (Å) Observed variants
1850 0 C1850S, C1850S,
1855 10
1803 14
1814 11
1794 8
1849 4 H1849R,
1856 10
1806 9 p.Thr1806SerfsX27,
1853 6 I1853V,
1795 7 Y1795N, Y1795H, Y1795C, p.Y1795_E1796insD,
1813 13
1818 13
1801 12
1838 14
1802 10
1820 15 A1820T, A1820V,
1504 9 K1504E,
1811 14 Y1811X, Y1811N,
1843 12
1851 4 M1851I, M1851I, M1851V, M1851I,
1501 9 L1501V, p.L1501_K1505del,
1857 10
1507 11 p.Q1507_P1509del,
1505 9 p.K1505_Q1507del, K1505N, K1505N,
1858 12
1509 15 P1509T,
1808 7
1835 15 L1835F,
1804 14
1807 6 c.5420dupA,
1821 13
1798 6 W1798X,
1854 6
1825 13 L1825P,
1797 12 I1797V,
1800 14
1793 14 M1793K,
1848 7
1817 10
1846 15
1498 14 M1498T, M1498R, M1498V,
1839 13 D1839G,
1796 13
1799 12
1500 14 p.K1500del,
1859 15
1791 11
1852 6 D1852V,
1792 13 D1792N, D1792V, D1792Y,
1508 15
1502 10 G1502S, G1502A,
1805 10
1842 13 M1842V, M1842L, M1842T, M1842L,
1810 13
1497 15
1790 15 D1790G, p.D1790del, D1790N,
1809 8 I1809M,
1506 8 P1506T, P1506S,
1841 11
1503 11 S1503Y,
1847 11 R1847H, R1847C,
1840 11