SCN5A Variant G292S

Summary of observed carriers, functional annotations, and structural context for SCN5A G292S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

1/27 effective observations

Estimated BrS1 penetrance

12%

3/27 effective observations

Total carriers

17

2 BrS1 · 1 LQT3 · 14 unaffected

G292S is present in 10 alleles in gnomAD. This residue resides in a Non_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 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
0.02 0.002 0.05 0.632 8 11

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
15277732 2004 6 0 2 0
30246897 2018 1 1 0 0
Literature, cohort, and gnomAD – 17 14 1 2 –
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)
15277732 2004
30246897 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 G292S.
Neighbour residue Distance (Å) Observed variants
277 15
278 14 H278R, H278D,
279 14
280 13 C280Y,
281 13 V281M,
282 12 R282C, R282H,
283 11
284 11
285 10 T285K,
286 9 A286V, A286S,
287 8
288 8 N288S,
289 7 G289S,
290 5 p.T290_G292del,
291 4 N291S, p.N291TfsX52, N291H, N291K, p.N291_S293dup, N291K
292 0 G292S,
293 4
294 5 V294M,
295 7 E295K,
296 8
297 8
298 9 G298S, G298D,
299 10 L299M, L299F, L299F,
300 11 V300I,
301 11
302 12
303 13
304 13
305 14 D305N,
306 14 L306F, L306V,
307 15