SCN5A Variant N470K

Summary of observed carriers, functional annotations, and structural context for SCN5A N470K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/15 effective observations

Estimated BrS1 penetrance

3%

0/15 effective observations

Total carriers

5

0 BrS1 · 0 LQT3 · 5 unaffected

N470K is present in 4 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 (%)
-1.62 0.002 2 0.274 3 2

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
18378609 2008 2 0 0 2 AF
22818067 2012 4 0 0 3 AF
Literature, cohort, and gnomAD – 5 5 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)
18378609 2008
22818067 2012

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 N470K.
Neighbour residue Distance (Å) Observed variants
455 15
456 14 V456M,
457 14
458 13 R458C, R458H, p.R458VfsX12,
459 13 S459G,
460 12
461 11 L461V,
462 11 E462A, E462K,
463 10 M463R, M463T
464 9
465 8 p.P465LfsX5,
466 8 L466F, L466F,
467 7
468 5 P468L,
469 4 V469I,
470 0 N470K, N470K,
471 4
472 5
473 7 E473X,
474 8 R474G, R474K,
475 8 R475S, R475K, R475S,
476 9
477 10 c.1428_1431delCAAG,
478 11
479 11
480 12 K480N, K480N,
481 13 R481W, R481Q,
482 13 M482I, M482I, M482I,
483 14
484 14
485 15