SCN5A Variant c.-53+1G>A

Summary of observed carriers, functional annotations, and structural context for SCN5A c.-53+1G>A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/15 effective observations

Estimated BrS1 penetrance

50%

7/15 effective observations

Total carriers

5

4 BrS1 · 0 LQT3 · 1 unaffected

c.-53+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 3 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 49 5

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
28781330 2017 5 0 4 0
Literature, cohort, and gnomAD – 5 1 0 4 –
Variant features alone – 15 12 0 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)
28781330 2017

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.-53+1G>A.
Neighbour residue Distance (Å) Observed variants
1 0 c.-53+1G>A, M1I,
2 4 A2T,
3 5 N3S, N3K, N3K,
4 7 F4V,
5 8
6 8 L6S,
7 9 P7R, P7L,
8 10 R8W, R8Q, R8P,
9 11 G9S, G9V,
10 11 T10S, T10S,
11 12 S11R, S11R, S11R,
12 13
13 13
14 14 R14S, R14C, R14H,
15 14 R15G, R15T, R15M,
16 15 F16L, F16L, F16L