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SCN5A Variant V2016M

Summary of observed carriers, functional annotations, and structural context for SCN5A V2016M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/19 effective observations

Estimated BrS1 penetrance

13%

2/19 effective observations

Total carriers

9

1 BrS1 · 0 LQT3 · 8 unaffected

V2016M is present in 8 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 1 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 (%)
-0.41 0.999 0.68 0.782 5 0

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
24895455 2014 1 0 1 0
26282245 2016 1 0 0 1 sinus node disfunction
28069705 2017 1 0 0 1 ARVD
Literature, cohort, and gnomAD – 9 8 0 1 –
Variant features alone – 15 14 0 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)
26282245 2016 HEK 55 0.8 -1.8 83
24895455 2014 51 3.7 0
28069705 2017
24895456 2014

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