SCN5A Variant p.F1486del

Summary of observed carriers, functional annotations, and structural context for SCN5A p.F1486del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

76%

4/11 effective observations

Estimated BrS1 penetrance

13%

1/11 effective observations

Total carriers

0 BrS1 · 1 LQT3 · 0 unaffected

p.F1486del 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 3 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density BrS (%)	Penetrance Density LQT3 (%)
NA	NA	NA	None	1	87

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
19419784	2010	1		1	0	0
20541041	2010	1		1	0	0
30059973	2018	1		1	0	0
Literature, cohort, and gnomAD	–	1	0	1	0		–
Variant features alone	–	15	11	3	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)
22826127	2012	HEK	20	0	10	2957
19419784	2010
20541041	2010
30059973	2018

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 p.F1486del.
Neighbour residue	Distance (Å)	Observed variants
1875	12	M1875K, M1875T, p.M1875dup
1872	14	K1872N, K1872N,
1496	13
1474	15
1491	6	Q1491H, Q1491H,
1481	12	G1481R, G1481R, G1481E, G1481V,
1874	13
1493	11	p.K1493del, K1493X, K1493R,
1484	8
1486	0	F1486L, p.F1486del, F1486L, F1486L,
1478	11	K1478E,
1488	6	T1488R,
1475	14	p.Q1475NfsX6, Q1475L,
1490	9
1498	15	M1498V, M1498T, M1498R,
1483	6	Q1483H, Q1483H,
1485	4
1494	11
1487	7	M1487L, M1487L, M1487K,
1495	10	Y1495S,
1869	14
1876	14
1479	15
1482	10
1489	9	E1489D, E1489D,
1492	8
1868	15