SCN5A Variant P2008L

Summary of observed carriers, functional annotations, and structural context for SCN5A P2008L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0/16 effective observations

Estimated BrS1 penetrance

0/16 effective observations

Total carriers

0 BrS1 · 0 LQT3 · 6 unaffected

P2008L is present in 6 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 (%)
-2.48	0.017	-2.41	0.386	2	8

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	–	6	6	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 P2008L.
Neighbour residue	Distance (Å)	Observed variants
1993	15
1994	14
1995	14	Y1995X,
1996	13	S1996N, S1996R,
1997	13	H1997R,
1998	12
1999	11
2000	11	D2000Y,
2001	10
2002	9	A2002T,
2003	8	D2003N,
2004	8	F2004V, F2004L, p.F2004dup, F2004I,
2005	7	P2005L, P2005S, P2005A,
2006	5	P2006T, p.Pro2006del, P2006A, p.P2006LfsX32,
2007	4	p.S2007FfsX7,
2008	0	P2008L,
2009	4	D2009E,
2010	5	R2010G,
2011	7
2012	8	R2012H, R2012C
2013	8
2014	9
2015	10
2016	11	V2016M, V2016L,