SCN5A Variant S524Y

Summary of observed carriers, functional annotations, and structural context for SCN5A S524Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/1179 effective observations

Estimated BrS1 penetrance

0%

2/1179 effective observations

Total carriers

1169

0 BrS1 · 0 LQT3 · 1169 unaffected

S524Y is present in 1150 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
-2.55 0.959 -1.03 None 29 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
16453024 2006 3 0 0 2 SIDS
23571586 2013 1 0 0 1 stillbirth, SUDS
20129283 2010 18 0 0 0
Literature, cohort, and gnomAD – 1169 1169 0 0 –
Variant features alone – 15 13 0 2 – –

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 84 -1 -2
17331104 2007 HEK 113 -5 1.6
15851227 2004
15898185 2004
16453024 2006
23571586 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 S524Y.
Neighbour residue Distance (Å) Observed variants
509 15
510 14
511 14
512 13 T512I,
513 13 R513C, c.1537delC, R513H, R513P,
514 12 G514C,
515 11
516 11
517 10 R517S, R517S,
518 9
519 8 S519F,
520 8 M520V, M520R,
521 7 K521E, c.1562delA,
522 5 P522S,
523 4 R523S, R523C, R523H,
524 0 c.1570_1571insG, S524Y,
525 4 S525G,
526 5 R526C, R526H,
527 7 G527R, G527R,
528 8 S528R, S528R, S528R,
529 8
530 9 F530V, F530S,
531 10 T531A, T531I,
532 11 F532L, F532C, F532L, F532L,
533 11 R533S, R533C, R533H,
534 12
535 13 R535G, R535X, R535Q,
536 13 D536H,
537 14
538 14 G538D
539 15