SCN5A Variant E161K
Summary of observed carriers, functional annotations, and structural context for SCN5A E161K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
6%
1/23 effective observations
Estimated BrS1 penetrance
68%
15/23 effective observations
Total carriers
13
11 BrS1 · 1 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.45 | 0.999 | -2.88 | 0.961 | 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
| Source | Year | Carriers | Unaffected | LQT3 | BrS1 | Other | Other Disease |
|---|---|---|---|---|---|---|---|
| 15910881 | 2005 | 11 | 0 | 9 | 2 | SSS, conduction disease | |
| 12106943 | 2002 | 1 | 0 | 1 | 0 | ||
| 16764707 | 2006 | 10 | 0 | 10 | 0 | ||
| 19843921 | 2009 | 1 | 0 | 1 | 0 | ||
| 20031634 | 2009 | 11 | 0 | 7 | 0 | ||
| 20386770 | 2010 | 1 | 1 | 0 | 0 | AV block | |
| 21273195 | 2011 | 8 | 0 | 8 | 0 | ||
| 19251209 | 2009 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29574140 | 2018 | 1 | 0 | 1 | 0 | ||
| 30059973 | 2018 | 2 | 2 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 13 | 1 | 1 | 11 | – | |
| 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.
| PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
|---|---|---|---|---|---|---|
| 20384651 | 2010 | HEK | 23 | 19.1 | 1.9 | |
| 15910881 | 2005 | tsA201 | 40 | 11.9 | 0.9 | |
| 12106943 | 2002 | |||||
| 16764707 | 2006 | |||||
| 19843921 | 2009 | |||||
| 20031634 | 2009 | |||||
| 20386770 | 2010 | |||||
| 21273195 | 2011 | |||||
| 20539757 | 2010 | |||||
| 19251209 | 2009 | |||||
| 15878172 | 2005 | |||||
| 20129283 | 2010 | |||||
| 20129283 | 2010 | |||||
| 29574140 | 2018 | |||||
| 30059973 | 2018 |
Nearby variants
Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.
| 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, |