SCN5A Variant K1505N

Summary of observed carriers, functional annotations, and structural context for SCN5A K1505N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

63%

4/12 effective observations

Estimated BrS1 penetrance

12%

1/12 effective observations

Total carriers

0 BrS1 · 2 LQT3 · 0 unaffected

K1505N has not been reported in gnomAD. This residue resides in a Mild_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 (%)
-4.6	0.68	-1.06	0.728	15	62

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
22360817	2012	1		1	0	0
19716085	2009	1		1	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). V_1/2 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)	V_1/2 Activation (mV)	V_1/2 Inactivation (mV)	Late/Persistent Current (% WT)
19716085	2009
22360817	2012

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 K1505N.
Neighbour residue	Distance (Å)	Observed variants
1850	9	C1850S, C1850S,
1794	12
1849	11	H1849R,
1806	11	p.Thr1806SerfsX27,
1853	14	I1853V,
1795	8	Y1795C, p.Y1795_E1796insD, Y1795N, Y1795H,
1802	13
1504	6	K1504E,
1851	9	M1851I, M1851V, M1851I, M1851I,
1501	11	L1501V, p.L1501_K1505del,
1507	8	p.Q1507_P1509del,
1505	0	K1505N, K1505N, p.K1505_Q1507del,
1509	13	P1509T,
1808	13
1804	15
1807	8	c.5420dupA,
1798	11	W1798X,
1854	12
1499	13
1796	13
1799	12
1788	13	c.5361_5364delTGAG,
1500	12	p.K1500del,
1791	12
1852	14	D1852V,
1792	12	D1792N, D1792V, D1792Y,
1508	9
1502	9	G1502S, G1502A,
1805	10
1506	5	P1506T, P1506S,
1503	7	S1503Y,