SCN5A Variant F543L

Summary of observed carriers, functional annotations, and structural context for SCN5A F543L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

62%

6/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

F543L has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 5 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 (%)
-4.61 0.983 -1.23 0.79 87 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
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 10 0 5 – –

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)
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 F543L.
Neighbour residue Distance (Å) Observed variants
528 15 S528R, S528R, S528R,
529 14
530 14 F530S, F530V,
531 13 T531I, T531A,
532 13 F532C, F532L, F532L, F532L,
533 12 R533H, R533C, R533S,
534 11
535 11 R535X, R535G, R535Q,
536 10 D536H,
537 9
538 8 G538D,
539 8
540 7
541 5
542 4
543 0 F543L, F543L, F543L,
544 4
545 5
546 7
547 8
548 8
549 9
550 10
551 11 A551T, A551V,
552 11 G552R, G552W, G552R,
553 12 E553K, E553X,
554 13 S554I, S554N,
555 13 E555K,
556 14
557 14 H557Q, H557L, H557Y, H557Q,
558 15 H558R,