SCN5A Variant P2005A

Summary of observed carriers, functional annotations, and structural context for SCN5A P2005A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/11 effective observations

Estimated BrS1 penetrance

8%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

P2005A has not been reported 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 (%)
-0.23 0.005 -0.28 0.236 6 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
26412604 2016 1 0 0 0
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.

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)
26412604 2016

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 P2005A.
Neighbour residue Distance (Å) Observed variants
1990 15 V1990L, V1990L,
1991 14 R1991W, R1991Q,
1992 14 G1992A,
1993 13
1994 13
1995 12 Y1995X,
1996 11 S1996R, S1996N, S1996R, S1996R,
1997 11 H1997R,
1998 10
1999 9
2000 8 D2000Y,
2001 8
2002 7 A2002T,
2003 5 D2003N,
2004 4 F2004I, F2004L, p.F2004dup, F2004V, F2004L,
2005 0 P2005A, P2005S, P2005L
2006 4 p.P2006LfsX32, p.Pro2006del, P2006T, P2006A,
2007 5 p.S2007FfsX7,
2008 7 P2008L,
2009 8 D2009E, D2009E,
2010 8 R2010G,
2011 9
2012 10 R2012C, R2012H,
2013 11
2014 11
2015 12
2016 13 V2016L, V2016M, V2016L,