SCN5A Variant L1825P

Summary of observed carriers, functional annotations, and structural context for SCN5A L1825P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

58%

4/12 effective observations

Estimated BrS1 penetrance

13%

1/12 effective observations

Total carriers

2

0 BrS1 · 2 LQT3 · 0 unaffected

L1825P has not been reported in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 2 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-6.47 1 -2.95 0.987 4 53

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
12208804 2002 1 0 0 1 diLQT
12835534 2003 1 0 0 1 diLQT
20541041 2010 2 2 0 0
Literature, cohort, and gnomAD – 2 0 2 0 –
Variant features alone – 15 12 2 1 – –

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)
29540853 2018 Xeno 25 -9.46
16301357 2005 CHO 11 0 -7.3 250
12208804 2002 HEK-tSA201 30 8.9 -11 867
12835534 2003
20541041 2010

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 L1825P.
Neighbour residue Distance (Å) Observed variants
1850 13 C1850S, C1850S,
1855 12
1814 12
1785 11
1794 7
1856 9
1853 10 I1853V,
1795 11 p.Y1795_E1796insD, Y1795N, Y1795H, Y1795C,
1828 10 A1828T, A1828S,
1834 13 S1834R, S1834R, S1834R,
1818 8
1801 14
1866 14
1824 4 P1824A,
1838 12
1820 9 A1820T, A1820V,
1504 14 K1504E,
1641 14
1863 11
1851 14 M1851I, M1851V, M1851I, M1851I,
1501 12 L1501V, p.L1501_K1505del,
1860 8 c.5577_5578dupAA,
1857 6
1862 10
1858 7
1829 14
1865 12
1787 10 S1787N,
1835 12 L1835F,
1819 10 D1819N,
1786 8 L1786Q, c.5356_5357delCT, L1786R,
1861 6 V1861I, V1861F,
1864 10
1815 13
1821 5
1798 12 W1798X,
1826 7 R1826C, R1826H,
1854 9
1825 0 L1825P,
1797 10 I1797V,
1793 9 M1793K,
1781 15 E1781D, E1781G, E1781D,
1789 11
1817 9
1784 14 E1784K, E1784X,
1827 7
1498 14 M1498R, M1498T, M1498V,
1796 13
1788 13 c.5361_5364delTGAG,
1500 13 p.K1500del,
1859 11
1791 8
1852 14 D1852V,
1792 11 D1792Y, D1792V, D1792N,
1823 7 p.E1823HfsX10, E1823K,
1783 15
1816 14 D1816E, D1816E, c.5445_5446insT, D1816N,
1831 13
1497 12
1790 7 D1790G, D1790N, p.D1790del,
1840 14
1822 5 c.5464_5467delTCTG, c.5464-5467delTCTG,
1782 14