SCN5A Variant K480N

Summary of observed carriers, functional annotations, and structural context for SCN5A K480N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/14 effective observations

Estimated BrS1 penetrance

4%

0/14 effective observations

Total carriers

4

0 BrS1 · 0 LQT3 · 4 unaffected

K480N is present in 2 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 (%)
-2.88 0.983 0.11 0.524 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
27287068 2016 2 0 0 0
Literature, cohort, and gnomAD – 4 4 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)
27287068 2016 Oocytes 110

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 K480N.
Neighbour residue Distance (Å) Observed variants
465 15 p.P465LfsX5,
466 14 L466F, L466F,
467 14
468 13 P468L,
469 13 V469I,
470 12 N470K, N470K,
471 11
472 11
473 10 E473X,
474 9 R474G, R474K,
475 8 R475K, R475S, R475S,
476 8
477 7 c.1428_1431delCAAG,
478 5
479 4
480 0 K480N, K480N,
481 4 R481W, R481Q,
482 5 M482I, M482I, M482I,
483 7
484 8
485 8
486 9 T486A, T486S, T486S,
487 10
488 11
489 11
490 12 G490E, G490A,
491 13 E491G,
492 13
493 14 R493K
494 14
495 15