SCN5A Variant c.703+1G>A

Summary of observed carriers, functional annotations, and structural context for SCN5A c.703+1G>A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

25%

1/12 effective observations

Estimated BrS1 penetrance

20%

2/12 effective observations

Total carriers

2

0 BrS1 · 1 LQT3 · 1 unaffected

c.703+1G>A has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 29 17

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
26669661 2016 2 1 0 0
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD – 2 1 1 0 –
Variant features alone – 15 13 0 2 – –

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)
26669661 2016
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.703+1G>A.
Neighbour residue Distance (Å) Observed variants
848 14 I848F
937 13
839 12 L839P,
842 10
240 9 V240M,
231 9 c.692_693delCA,
193 15 W193R, W193R, W193X,
237 6
228 14 K228R,
836 12 V836M,
234 4 P234S,
229 13
933 14
845 11 c.2533delG,
232 9 V232I, V232F,
244 14
420 11
241 10
235 0 c.703+1G>A, G235R, G235R, c.704-1G>C,
840 10
843 13 T843A,
419 10 Q419X,
423 10
834 15 N834D,
837 8
239 7 I239V, I239V ,
230 10 I230V, I230T, I230M,
242 11 A242D,
416 12 Y416C,
841 6 p.N841TfsX2, N841K, N841K,
236 4
238 5
233 6
838 8
422 13
844 11 L844RfsX3,
243 13
835 12 S835A, S835L,