SCN5A Variant F777L

Summary of observed carriers, functional annotations, and structural context for SCN5A F777L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

9%

0/11 effective observations

Estimated BrS1 penetrance

55%

6/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

F777L 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 (%)
-5.93 0.166 1.38 0.839 80 9

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
25758664 2015 1 0 1 0
29907895 2018 1 0 0 1 SIDS
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)
25758664 2015
29907895 2018

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 F777L.
Neighbour residue Distance (Å) Observed variants
766 15
774 8 p.Y774TfsX28, Y774D, c.2320delT, Y774C,
784 11 F784L, F784L, F784L,
763 15 E763D, E763D, E763K,
778 7
772 9 D772N,
767 11
770 12
781 12 W781X,
775 9
771 9 L771V,
785 10 D785N,
783 5 I783T,
769 12
789 12 V789I, V789A,
773 5 P773S,
714 15 V714D, V714A,
780 8
776 4 p.Y776del,
788 13 I788V,
768 7
765 12
786 8
761 15
787 10
779 8 Q779K, Q779X,
764 10 M764R, M764K,
777 0 F777L, F777L, F777L,
782 6 N782T,
790 12