SCN5A Variant M1842L

Summary of observed carriers, functional annotations, and structural context for SCN5A M1842L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/12 effective observations

Estimated BrS1 penetrance

3%

0/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

M1842L is present in 2 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 (%)
-1.8 0.017 2.43 0.613 1 3

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 – 2 2 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 M1842L.
Neighbour residue Distance (Å) Observed variants
1852 9 D1852V,
1850 13 C1850S, C1850S,
1811 7 Y1811N, Y1811X,
1843 5
1814 10
1851 14 M1851I, M1851I, M1851I, M1851V,
1849 10 H1849R,
1856 14
1857 15
1842 0 M1842L, M1842T, M1842V, M1842L,
1806 14 p.Thr1806SerfsX27,
1853 11 I1853V,
1837 14
1848 6
1812 11 S1812L, S1812X,
1808 10
1810 10
1836 11 I1836T,
1813 12
1846 5
1835 12 L1835F,
1839 10 D1839G,
1809 10 I1809M,
1844 7
1807 14 c.5420dupA,
1841 5
1838 13
1847 7 R1847C, R1847H,
1845 7 G1845R, G1845R,
1832 13 Q1832E,
1840 7
1815 14