SCN5A Variant E161Q

Summary of observed carriers, functional annotations, and structural context for SCN5A E161Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/11 effective observations

Estimated BrS1 penetrance

51%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

E161Q 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 (%)
-2.59 0.997 -1.85 0.968 67 2

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

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 E161Q.
Neighbour residue Distance (Å) Observed variants
154 13 P154L,
223 13 V223L,
859 14
153 15
149 13
147 7
164 6 F164L, F164L, F164L,
209 14 N209S, N209T,
143 11
156 9 W156R, W156R, W156X,
158 6 K158T,
163 7 c.486delC,
216 15 S216X, S216L,
169 13
222 8 R222X, R222Q, R222L,
155 11
150 12
157 7 T157I,
160 5 p.V160fs,
205 12 c.612-2A>G, Y205X,
206 13
166 10 A166T,
144 8
855 15
148 10
165 7
210 13 I210T,
204 9 A204T, c.611+1G>A, c.611+3_611+4dupAA, A204V,
162 5 Y162H, Y162C,
146 13 V146M, V146A,
203 13
208 8 E208K,
168 10
202 15 I202T,
152 15 D152N,
141 13 I141V, I141N,
167 11
161 0 E161K, E161Q,
201 12
219 9 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
225 13 R225W, R225Q
151 9
218 12
159 7 Y159C, Y159X,
207 9
212 14 L212Q, L212P,
200 13
145 12
140 12
220 14 T220I,