SCN5A Variant D1816E

Summary of observed carriers, functional annotations, and structural context for SCN5A D1816E. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

10%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

D1816E is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-2.79 0.006 2.73 0.655 13 2

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 – 1 1 0 0 –
Variant features alone – 15 14 0 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 D1816E.
Neighbour residue Distance (Å) Observed variants
1803 15
1814 7
1794 13
1853 13 I1853V,
1828 10 A1828T, A1828S,
1834 14 S1834R, S1834R, S1834R,
1813 5
1818 6
1801 7
1802 13
1832 11 Q1832E,
1820 7 A1820V, A1820T,
1811 10 Y1811N, Y1811X,
1857 13
1812 8 S1812X, S1812L,
1829 7
1835 11 L1835F,
1819 6 D1819N,
1821 10
1815 4
1798 12 W1798X,
1826 12 R1826H, R1826C,
1825 14 L1825P,
1797 10 I1797V,
1800 11
1793 15 M1793K,
1848 13
1817 6
1827 10
1799 15
1816 0 c.5445_5446insT, D1816N, D1816E, D1816E,
1831 9
1810 10
1809 10 I1809M,
1830 11
1840 15
1822 13 c.5464_5467delTCTG, c.5464-5467delTCTG,