SCN5A Variant S330F

Summary of observed carriers, functional annotations, and structural context for SCN5A S330F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

21%

1/11 effective observations

Estimated BrS1 penetrance

13%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

S330F is present in 1 alleles in gnomAD. This residue resides in a 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 (%)
-5.29 0.966 -1.17 0.673 14 26

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 S330F.
Neighbour residue Distance (Å) Observed variants
328 8
333 8 c.998+1G>A, c.998+5G>A,
1702 13
326 12
387 7
385 9 A385T,
391 15
330 0 S330F,
278 14 H278D, H278R,
388 8 I388S,
1698 11 A1698T
334 9 c.999-424_1338+81del,
332 6 A332T,
327 10
384 11 S384T,
329 4
1692 13
386 8 G386R, G386R, G386E,
1693 14
1699 11
331 4
341 14 C341Y,
335 12 C335S, C335R, C335S,
325 15 L325R,
1228 13 Y1228H, Y1228C, Y1228F,
1690 14 c.5068_5070delGA, D1690N,
1697 13
389 11 Y389H, Y389X,
390 13
275 15 N275K, N275K,
383 12
1614 15
382 10
1696 13
1689 15 D1689N,
381 13 c.1140+1G>A, c.1141-3C>A,
1691 10