SCN5A Variant N592K

Summary of observed carriers, functional annotations, and structural context for SCN5A N592K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/21 effective observations

Estimated BrS1 penetrance

13%

2/21 effective observations

Total carriers

11

1 BrS1 · 0 LQT3 · 10 unaffected

N592K 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 (%)
-2.54 0.684 -0.28 0.821 4 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
24463578 2014 2 0 1 0
26154754 2015 1 0 1 0
20129283 2010 1 0 0 0
Literature, cohort, and gnomAD – 11 10 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)
24463578 2014 HEK 17 3.2 1.2
26154754 2015
20129283 2010

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 N592K.
Neighbour residue Distance (Å) Observed variants
577 15 S577N,
578 14 P578R, P578T,
579 14 G579R, G579R
580 13
581 13 S581L,
582 12
583 11 P583L,
584 11 G584R,
585 10
586 9 A586G, p.586_587delAL, A586T,
587 8
588 8 H588R, H588N,
589 7
590 5 K590Q,
591 4
592 0 N592K, N592K, N592S,
593 4
594 5
595 7
596 8 D596G,
597 8 C597G, C597Y,
598 9
599 10 G599R, G599R,
600 11
601 11 V601A,
602 12
603 13
604 13 L604V,
605 14 G605E,
606 14 A606T,
607 15 G607V, G607D, G607R,