SCN5A Variant G319S

Summary of observed carriers, functional annotations, and structural context for SCN5A G319S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

1/26 effective observations

Estimated BrS1 penetrance

9%

2/26 effective observations

Total carriers

16

1 BrS1 · 1 LQT3 · 14 unaffected

G319S is present in 14 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 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 (%)
-5.29 0.058 -0.87 0.79 13 2

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
11076825 2000 1 0 1 0
11901046 2002 1 0 1 0
16712702 2006 1 0 0 1 Sudden adult death syndrome
24606995 2014 1 1 0 0
Literature, cohort, and gnomAD – 16 14 1 1 –
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)
11076825 2000
11901046 2002
16712702 2006
24606995 2014

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 G319S.
Neighbour residue Distance (Å) Observed variants
287 14
341 15 C341Y,
342 12
339 12
346 13 E346K, E346G, E346D, E346D, E346X,
319 0 G319C, G319R, G319S,
317 7 K317E, K317N, K317M, K317N,
284 10
282 8 R282C, R282H,
279 11
321 7 S321Y,
344 11 A344S,
340 12 R340W, R340Q,
285 9 T285K,
338 13
345 11
322 11
280 11 C280Y,
318 5
281 8 V281M,
323 11
283 10
286 13 A286V, A286S,
320 3 T320N,