SCN5A Variant R481W

Summary of observed carriers, functional annotations, and structural context for SCN5A R481W. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

1/370 effective observations

Estimated BrS1 penetrance

0%

1/370 effective observations

Total carriers

360

1 BrS1 · 1 LQT3 · 358 unaffected

R481W is present in 352 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 (%)
-4.62 0.009 0.47 None 2 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
23293604 2012 1 0 1 0
23714088 2013 1 1 0 0
20129283 2010 6 0 0 0
Literature, cohort, and gnomAD – 360 358 1 1 –
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)
15992732 2005 HEK 137 1 -6
15851227 2004
15898185 2004
23293604 2012
23714088 2013
15992733 2005
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 R481W.
Neighbour residue Distance (Å) Observed variants
466 15 L466F, L466F,
467 14
468 14 P468L,
469 13 V469I
470 13 N470K, N470K,
471 12
472 11
473 11 E473X,
474 10 R474G, R474K,
475 9 R475S, R475K, R475S,
476 8
477 8 c.1428_1431delCAAG,
478 7
479 5
480 4 K480N, K480N,
481 0 R481W, R481Q,
482 4 M482I, M482I, M482I,
483 5
484 7
485 8
486 8 T486A, T486S, T486S,
487 9
488 10
489 11
490 11 G490E, G490A,
491 12 E491G,
492 13
493 13 R493K,
494 14
495 14
496 15 K496N, K496N, K496M,