SCN5A Variant F733L

Summary of observed carriers, functional annotations, and structural context for SCN5A F733L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/12 effective observations

Estimated BrS1 penetrance

24%

2/12 effective observations

Total carriers

2

0 BrS1 · 0 LQT3 · 2 unaffected

F733L is present in 2 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 2 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 (%)
-5.7 0.049 -0.88 0.95 39 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
Literature, cohort, and gnomAD – 2 2 0 0 –
Variant features alone – 15 13 0 2 – –

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 F733L.
Neighbour residue Distance (Å) Observed variants
723 15 I723V,
758 14 G758E,
742 14 T742A,
811 10 R811G, R811H, c.2435_2436+3delTGGTAinsCGCCT,
733 0 F733L,
741 13 p.M741_T742delinsI ,
808 13 R808C, R808H, R808P,
745 10
746 12 E746K,
760 13 p.F760SfsX5,
812 13 L812Q,
1350 11 I1350L, I1350T,
759 13 I759V, c.2274delG, p.I759FfsX6,
792 15
755 10
731 7 T731I,
754 11
726 10
818 15
1353 13 V1353M,
737 9
1404 15
750 10 Q750R,
1349 15
749 6
743 15
1346 14 L1346I, L1346P,
724 14 T724I,
728 9 V728I,
747 12 E747A,
727 10
735 7 A735V, A735E, A735T,
732 5
734 6 c.2201dupT, M734V,
756 8
814 11 R814Q,
757 12
1354 13
744 14
738 13
752 6 G752R,
1405 13 V1405M, V1405L,
815 13
725 13
751 9 V751I, V751F,
736 7 L736P,
730 5 N730K,
753 7
729 6 p.L729del,
748 7 M748I,