SCN5A Variant A124D

Summary of observed carriers, functional annotations, and structural context for SCN5A A124D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/11 effective observations

Estimated BrS1 penetrance

49%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

A124D 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 (%)
-5.23 0.986 -6.34 0.936 59 1

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
22529811 2012 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)
22529811 2012 tsA201 23 3.6 3.2

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 A124D.
Neighbour residue Distance (Å) Observed variants
126 6 K126E,
136 15 L136P,
175 9 K175N, K175N,
129 8
188 14
178 6 A178G,
128 6 c.381dupT,
117 14
179 9 R179X, R179Q,
119 9 P119S, P119L,
169 14
177 6 L177P,
123 4 A123G, A123V,
121 6 R121W, R121Q,
127 5
124 0 A124D,
118 11
125 4 V125L, V125L,
181 15
176 10
172 11
131 14
174 6 V174I,
133 10
115 12 S115G,
173 9
132 14 c.393-5C>A,
114 11
130 10
184 14 H184R
116 12
180 11 G180V,
134 12 N134S,
170 10 F170I,
120 7
122 8
171 11
137 14 I137V,