SCN5A Variant G298S

Summary of observed carriers, functional annotations, and structural context for SCN5A G298S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/17 effective observations

Estimated BrS1 penetrance

7%

1/17 effective observations

Total carriers

7

0 BrS1 · 0 LQT3 · 7 unaffected

G298S is present in 7 alleles in gnomAD. This residue resides in a Non_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 (%)
-0.47 0.824 -0.21 0.551 3 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
11804990 2002 1 0 0 1 AV block
Literature, cohort, and gnomAD – 7 7 0 0 –
Variant features alone – 15 14 0 1 – –

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)
19056759 2009 HEK 50
11804990 2002 HEK-tSA204 85 3.6 7.4

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 G298S.
Neighbour residue Distance (Å) Observed variants
283 15
284 14
285 14 T285K,
286 13 A286V, A286S,
287 13
288 12 N288S,
289 11 G289S,
290 11 p.T290_G292del,
291 10 N291S, p.N291TfsX52, N291H, N291K, p.N291_S293dup, N291K
292 9 G292S,
293 8
294 8 V294M,
295 7 E295K,
296 5
297 4
298 0 G298S, G298D,
299 4 L299M, L299F, L299F,
300 5 V300I,
301 7
302 8
303 8
304 9
305 10 D305N,
306 11 L306F, L306V,
307 11
308 12
309 13 S309N, S309C,
310 13 D310N,
311 14
312 14 E312K, c.934+4C>T, c.934+1G>A,
313 15