SCN5A Variant A178G

Summary of observed carriers, functional annotations, and structural context for SCN5A A178G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

49%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

A178G 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 4 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 (%)
-3.85 0.997 1.11 0.946 78 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
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 11 0 4 – –

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)
20129283 2010
32533946 2020 HEK 110 9.2

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 A178G.
Neighbour residue Distance (Å) Observed variants
170 12 F170I,
126 10 K126E,
175 7 K175N, K175N,
197 14
113 11 V113I, V113A,
129 9
194 12
188 9
178 0 A178G,
128 7 c.381dupT,
117 13
179 3 R179X, R179Q,
119 12 P119S, P119L,
169 15
177 5 L177P,
189 15
123 9 A123G, A123V,
121 5 R121W, R121Q,
198 13
127 9
124 6 A124D,
118 11
125 5 V125L, V125L,
181 11
176 6
172 10
174 6 V174I,
185 11 A185T, A185V,
133 12
115 10 S115G,
130 13
182 13 C182R, C182Y,
173 9
112 11 Y112C,
114 8
184 8 H184R,
191 15
116 10
187 12 T187S, T187S, T187I
180 6 G180V,
134 13 N134S,
120 10
183 13
122 9
171 11