SCN5A Variant c.934+1G>A

Summary of observed carriers, functional annotations, and structural context for SCN5A c.934+1G>A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/13 effective observations

Estimated BrS1 penetrance

67%

8/13 effective observations

Total carriers

3

3 BrS1 · 0 LQT3 · 0 unaffected

c.934+1G>A has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 5 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 (%)
NA NA NA None 88 0

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
21135007 2011 3 0 1 2 RBBB, conduction
21273195 2011 1 0 1 0
22885917 2012 2 0 2 0
26921764 2016 2 0 2 0
20129283 2010 1 0 1 0
29325976 2018 1 0 1 0
29759671 2018 1 0 1 0
30059973 2018 2 2 0 0
Literature, cohort, and gnomAD – 3 0 0 3 –
Variant features alone – 15 10 0 5 – –

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)
21135007 2011
21273195 2011
22885917 2012
26921764 2016
20129283 2010
29325976 2018
29759671 2018
30059973 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 c.934+1G>A.
Neighbour residue Distance (Å) Observed variants
297 15
298 14 G298S, G298D,
299 14 L299M, L299F, L299F,
300 13 V300I,
301 13
302 12
303 11
304 11
305 10 D305N,
306 9 L306F, L306V,
307 8
308 8
309 7 S309N, S309C,
310 5 D310N,
311 4
312 0 E312K, c.934+4C>T, c.934+1G>A,
313 4
314 5
315 7 L315P,
316 8
317 8 K317M, K317N, K317N, K317E,
318 9
319 10 G319R, G319S, G319C,
320 11 T320N,
321 11 S321Y,
322 12
323 13
324 13
325 14 L325R,
326 14
327 15