SCN5A Variant S216L
Summary of observed carriers, functional annotations, and structural context for SCN5A S216L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
2%
4/200 effective observations
Estimated BrS1 penetrance
1%
2/200 effective observations
Total carriers
190
1 BrS1 · 4 LQT3 · 185 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.84 | 0.982 | -3.76 | 0.958 | 9 | 8 |
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 |
|---|---|---|---|---|---|---|---|
| 21705349 | 2011 | 1 | 0 | 1 | 0 | ||
| 17210841 | 2007 | 1 | 0 | 0 | 1 | SIDS | |
| 27287068 | 2016 | 3 | 3 | 0 | 0 | ||
| 19412328 | 2008 | 1 | 0 | 0 | 1 | DCM | |
| 22677073 | 2012 | 1 | 0 | 0 | 1 | SUDS | |
| 23321620 | 2013 | 1 | 0 | 1 | 0 | ||
| 24667783 | 2015 | 1 | 1 | 0 | 0 | ||
| 25163546 | 2015 | 1 | 0 | 0 | 1 | DCM | |
| 22685113 | 2012 | 2 | 0 | 0 | 2 | AF | |
| 20129283 | 2010 | 4 | 0 | 0 | 0 | ||
| 29672598 | 2018 | 1 | 0 | 0 | 1 | SUDS | |
| Literature, cohort, and gnomAD | – | 190 | 185 | 4 | 1 | – | |
| Variant features alone | – | 15 | 14 | 0 | 1 | – | – |
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) |
|---|---|---|---|---|---|---|
| 21705349 | 2011 | HEK-tSA201 | 40 | 1 | 1 | 83 |
| 17210841 | 2007 | tsA205 | 100 | -0.2 | 4.7 | 777 |
| 27287068 | 2016 | Oocytes | 130 | |||
| 19412328 | 2008 | |||||
| 22378279 | 2012 | |||||
| 22677073 | 2012 | |||||
| 23321620 | 2013 | |||||
| 24667783 | 2015 | |||||
| 25163546 | 2015 | |||||
| 29017927 | 2017 | |||||
| 23465283 | 2013 | |||||
| 17646591 | 2007 | |||||
| 22685113 | 2012 | HEK | ||||
| 20129283 | 2010 | |||||
| 29672598 | 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 |
|---|---|---|
| 223 | 13 | V223L, |
| 856 | 11 | V856L, V856L, |
| 862 | 11 | |
| 867 | 14 | E867K, E867Q, E867X, |
| 859 | 7 | |
| 209 | 14 | N209S, N209T, |
| 863 | 10 | |
| 156 | 15 | W156R, W156R, W156X, |
| 864 | 12 | |
| 216 | 0 | S216X, S216L, |
| 221 | 9 | |
| 222 | 10 | R222X, R222Q, R222L, |
| 224 | 14 | L224F, |
| 213 | 8 | |
| 857 | 11 | G857D, |
| 881 | 15 | |
| 860 | 8 | p.L860fsx89, |
| 206 | 11 | |
| 214 | 7 | |
| 858 | 12 | M858L, M858L, |
| 211 | 11 | |
| 217 | 4 | |
| 855 | 13 | |
| 913 | 14 | |
| 148 | 15 | |
| 210 | 13 | I210T, |
| 204 | 12 | A204T, c.611+1G>A, c.611+3_611+4dupAA, A204V, |
| 910 | 13 | S910L |
| 203 | 10 | |
| 208 | 14 | E208K, |
| 202 | 15 | I202T, |
| 161 | 15 | E161K, E161Q, |
| 219 | 6 | p.R219HfsX11, R219C, c.656_657insATTCA, R219H, |
| 151 | 14 | |
| 218 | 6 | |
| 207 | 9 | |
| 212 | 8 | L212Q, L212P, |
| 215 | 4 | p.L215CfsX10, |
| 914 | 12 | |
| 200 | 14 | |
| 861 | 11 | p.F861WfsX90, c.2582_2583delTT, |
| 220 | 6 | T220I, |