SCN5A Variant F816L

Summary of observed carriers, functional annotations, and structural context for SCN5A F816L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

18%

1/11 effective observations

Estimated BrS1 penetrance

12%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

F816L is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-5.94 0.983 3.55 0.853 15 17

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 13 1 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 F816L.
Neighbour residue Distance (Å) Observed variants
723 15 I723V,
811 13 R811G, R811H, c.2435_2436+3delTGGTAinsCGCCT,
821 11
1340 11 V1340I,
1339 13 L1339F, p.L1339del
1351 12 M1351V, M1351R,
760 14 p.F760SfsX5,
780 12
1452 14
812 7 L812Q,
1350 12 I1350T, I1350L,
792 15
791 14 L791F,
1344 8 F1344S, F1344L,
731 11 T731I,
819 7
826 11 N826D,
818 7
825 9
781 9 W781X,
1348 11 F1348L,
1349 14
822 12 W822X, W822C,
830 15
788 10 I788V,
1346 11 L1346I, L1346P,
833 14 G833R,
724 13 T724I,
782 14 N782T,
1341 14
728 13 V728I,
820 10
810 11
823 14 P823T,
727 11
1456 12
734 12 c.2201dupT, M734V,
827 14
814 9 R814Q,
1460 15 F1460L,
816 0 F816L, F816Y,
813 6 c.2436+12G>A, c.2437-5C>A,
786 14
817 7 K817E,
809 12
815 5
1343 9
1345 14 W1345C,
1342 13
784 8 F784L,
785 11 D785N,
783 14 I783T,
730 13 N730K,
789 14 V789A, V789I,
1347 7
824 13
829 9
787 12
832 12
828 11 L828V,