SCN5A Variant A1828S

Summary of observed carriers, functional annotations, and structural context for SCN5A A1828S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/11 effective observations

Estimated BrS1 penetrance

5%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

A1828S is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-1.2 0.027 -0.52 0.625 1 5

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 15 0 0 – –

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 A1828S.
Neighbour residue Distance (Å) Observed variants
1823 10 E1823K, p.E1823HfsX10,
1826 6 R1826H, R1826C,
1814 11
1816 10 D1816E, c.5445_5446insT, D1816N, D1816E,
1794 15
1856 15
1825 10 L1825P,
1860 10 c.5577_5578dupAA,
1857 11
1797 14 I1797V,
1853 15 I1853V,
1837 14
1831 6
1828 0 A1828T, A1828S,
1817 11
1829 5
1834 9 S1834R, S1834R, S1834R,
1836 14 I1836T,
1813 14
1827 4
1835 10 L1835F,
1818 7
1833 11 I1833M,
1819 5 D1819N,
1821 9
1861 13 V1861I, V1861F,
1824 11 P1824A,
1838 13
1832 11 Q1832E,
1830 6
1822 10 c.5464-5467delTCTG, c.5464_5467delTCTG,
1864 12
1820 9 A1820T, A1820V,
1815 8