SCN5A Variant F532L

Summary of observed carriers, functional annotations, and structural context for SCN5A F532L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/14 effective observations

Estimated BrS1 penetrance

9%

1/14 effective observations

Total carriers

4

0 BrS1 · 0 LQT3 · 4 unaffected

F532L 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 1 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 (%)
-3.55 0.963 -0.48 0.619 9 5

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
Literature, cohort, and gnomAD – 4 4 0 0 –
Variant features alone – 15 14 0 1 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 F532L.
Neighbour residue Distance (Å) Observed variants
517 15 R517S, R517S,
518 14
519 14 S519F,
520 13 M520V, M520R,
521 13 c.1562delA, K521E,
522 12 P522S,
523 11 R523H, R523C, R523S,
524 11 c.1570_1571insG, S524Y,
525 10 S525G,
526 9 R526H, R526C,
527 8 G527R, G527R,
528 8 S528R, S528R, S528R,
529 7
530 5 F530S, F530V,
531 4 T531I, T531A,
532 0 F532C, F532L, F532L, F532L,
533 4 R533H, R533C, R533S,
534 5
535 7 R535X, R535G, R535Q,
536 8 D536H,
537 8
538 9 G538D,
539 10
540 11
541 11
542 12
543 13 F543L, F543L, F543L,
544 13
545 14
546 14
547 15