SCN5A Variant L212Q
Summary of observed carriers, functional annotations, and structural context for SCN5A L212Q. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
25%
1/11 effective observations
Estimated BrS1 penetrance
40%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.82 | 0.999 | -2.77 | 0.98 | 41 | 39 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 1 | 3 | – | – |
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) |
|---|---|---|---|---|---|---|
| 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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 203 | 13 | |
| 208 | 10 | E208K, |
| 205 | 14 | Y205X, c.612-2A>G, |
| 156 | 14 | W156R, W156X, |
| 158 | 12 | K158T, |
| 859 | 13 | |
| 206 | 10 | |
| 216 | 8 | S216L, S216X, |
| 214 | 7 | |
| 161 | 14 | E161Q, E161K, |
| 219 | 10 | R219H, R219C, c.656_657insATTCA, p.R219HfsX11, |
| 211 | 5 | |
| 217 | 11 | |
| 222 | 14 | R222L, R222X, R222Q, |
| 218 | 9 | |
| 213 | 5 | |
| 207 | 7 | |
| 212 | 0 | L212Q, L212P, |
| 209 | 9 | N209T, N209S, |
| 215 | 9 | p.L215CfsX10, |
| 863 | 14 | |
| 210 | 5 | I210T, |
| 220 | 13 | T220I, |
| 204 | 12 | c.611+1G>A, c.611+3_611+4dupAA, A204V, A204T, |
| 162 | 14 | Y162C, Y162H, |