SCN5A Variant c.381dupT

Summary of observed carriers, functional annotations, and structural context for SCN5A c.381dupT. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

61%

6/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.381dupT 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 5 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 86 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
26941339 2016 1 0 1 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 10 0 5 – –

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)
26941339 2016
20129283 2010

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.381dupT.
Neighbour residue Distance (Å) Observed variants
121 10 R121W, R121Q,
231 15 c.692_693delCA
198 13
124 6 A124D,
131 9
130 8
114 14
170 10 F170I,
184 14 H184R,
228 14 K228R,
138 13 M138I, M138I, M138I,
122 13
171 8
137 10 I137V,
197 12
129 4
169 14
177 10 L177P,
123 9 A123G, A123V,
127 5
125 6 V125L, V125L,
174 6 V174I,
133 6
132 10 c.393-5C>A,
134 7 N134S,
179 8 R179X, R179Q,
172 10
180 12 G180V,
120 13
126 8 K126E,
136 11 L136P,
168 14
175 6 K175N, K175N,
194 12
188 12
135 12 M135V,
167 13
178 7 A178G,
128 0 c.381dupT,
176 10
173 10