SCN5A Variant c.998+5G>A

Summary of observed carriers, functional annotations, and structural context for SCN5A c.998+5G>A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

41%

2/11 effective observations

Estimated BrS1 penetrance

31%

3/11 effective observations

Total carriers

1

0 BrS1 · 1 LQT3 · 0 unaffected

c.998+5G>A has not been reported 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 3 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 (%)
NA NA NA None 48 37

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
23631430 2013 1 1 0 0
Literature, cohort, and gnomAD 1 0 1 0
Variant features alone 15 11 1 3

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)
23631430 2013

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.998+5G>A.
Neighbour residue Distance (Å) Observed variants
328 8
333 0 c.998+5G>A, c.998+1G>A,
1702 12
326 6
276 14 L276P, L276Q,
387 10
279 14
385 9 A385T,
338 15
1687 13
330 8 S330F,
278 11 H278D, H278R,
388 13 I388S,
1698 13 A1698T,
334 3 c.999-424_1338+81del,
332 3 A332T,
327 6
339 13
1695 13 Q1695X,
384 8 S384T,
1688 13
1684 13 W1684R, W1684R,
329 7
1692 9
386 8 G386R, G386R, G386E,
1693 11
378 13
1699 10
331 6
379 11
1703 14
341 11 C341Y,
335 7 C335S, C335S, C335R,
325 9 L325R,
1690 8 D1690N, c.5068_5070delGA,
324 10
389 13 Y389H, Y389X,
390 15
275 14 N275K, N275K
383 5
280 11 C280Y,
323 13
382 8
337 14
1696 13
1689 8 D1689N,
342 15
336 10 P336L,
381 11 c.1141-3C>A, c.1140+1G>A,
1691 5
380 11