SCN5A Variant M1851I

Summary of observed carriers, functional annotations, and structural context for SCN5A M1851I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

8%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

M1851I 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 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 (%)
-0.53 0.525 -1.09 0.518 10 7

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 M1851I.
Neighbour residue Distance (Å) Observed variants
1850 4 C1850S, C1850S,
1855 8
1814 14
1794 10
1849 5 H1849R,
1856 10
1806 12 p.Thr1806SerfsX27,
1853 7 I1853V,
1795 9 Y1795N, Y1795H, Y1795C, p.Y1795_E1796insD,
1880 14 M1880V,
1838 14
1802 14
1504 9 K1504E,
1843 13
1851 0 M1851I, M1851I, M1851V, M1851I,
1501 7 L1501V, p.L1501_K1505del,
1857 11
1507 14 p.Q1507_P1509del,
1505 9 p.K1505_Q1507del, K1505N, K1505N,
1858 11
1808 10
1786 15 c.5356_5357delCT, L1786R, L1786Q,
1807 8 c.5420dupA,
1798 10 W1798X,
1854 5
1825 14 L1825P,
1848 10
1499 12
1817 14
1498 10 M1498T, M1498R, M1498V,
1839 12 D1839G,
1500 12 p.K1500del,
1859 13
1876 15
1791 11
1852 5 D1852V,
1792 14 D1792N, D1792V, D1792Y,
1502 7 G1502S, G1502A,
1805 13
1842 14 M1842V, M1842L, M1842T, M1842L,
1497 12
1809 12 I1809M,
1506 10 P1506T, P1506S,
1841 11
1503 9 S1503Y,
1847 14 R1847H, R1847C,
1840 11