SCN5A Variant F784L

Summary of observed carriers, functional annotations, and structural context for SCN5A F784L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/11 effective observations

Estimated BrS1 penetrance

17%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

F784L is present in 1 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 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 (%)
-5.94 0.036 1.63 0.774 24 1

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 – 1 1 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 F784L.
Neighbour residue Distance (Å) Observed variants
723 13 I723V,
811 14 R811H, R811G, c.2435_2436+3delTGGTAinsCGCCT,
821 13
760 11 p.F760SfsX5,
780 6
776 11 p.Y776del,
812 12 L812Q,
792 12
764 10 M764K, M764R,
777 11 F777L, F777L, F777L,
791 10 L791F,
819 10
826 13 N826D,
818 11
825 14
781 5 W781X,
720 14
788 6 I788V,
724 14 T724I,
782 7 N782T
793 15 L793F,
820 9
810 11
727 12
767 13
814 9 R814Q,
816 8 F816L, F816L, F816L, F816Y,
813 7 c.2436+12G>A, c.2437-5C>A,
757 14
768 14
786 7
817 7 K817E,
761 14
779 10 Q779K, Q779X,
809 14
815 10
778 14
790 11
784 0 F784L, F784L, F784L,
763 14 E763K, E763D, E763D,
785 4 D785N,
783 6 I783T,
730 15 N730K, N730K,
789 9 V789A, V789I,
1347 14
829 12
787 6
794 15