SCN5A Variant c.611+1G>A
Summary of observed carriers, functional annotations, and structural context for SCN5A c.611+1G>A. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
8%
1/21 effective observations
Estimated BrS1 penetrance
64%
13/21 effective observations
Total carriers
11
9 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 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 64 | 3 |
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 |
|---|---|---|---|---|---|---|---|
| 24606995 | 2014 | 1 | 1 | 0 | 0 | ||
| 26111534 | 2015 | 1 | 0 | 0 | 1 | SND, AF | |
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| 29709101 | 2018 | 9 | 0 | 8 | 0 | ||
| 30059973 | 2018 | 2 | 2 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 11 | 1 | 1 | 9 | – | |
| 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.
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 | 11 | V223L, |
| 859 | 13 | |
| 198 | 11 | |
| 147 | 14 | |
| 164 | 10 | F164L, |
| 209 | 8 | N209T, N209S, |
| 195 | 14 | |
| 171 | 13 | |
| 158 | 12 | K158T, |
| 197 | 12 | |
| 163 | 12 | c.486delC, |
| 216 | 12 | S216X, S216L, |
| 221 | 10 | |
| 196 | 13 | |
| 169 | 10 | |
| 222 | 6 | R222X, R222L, R222Q, |
| 224 | 12 | L224F, |
| 160 | 13 | p.V160fs, |
| 226 | 15 | A226V, A226G, |
| 205 | 6 | Y205X, c.612-2A>G, |
| 206 | 5 | |
| 166 | 10 | A166T, |
| 214 | 14 | |
| 211 | 12 | |
| 144 | 12 | |
| 217 | 10 | |
| 172 | 13 | |
| 199 | 9 | S199T, |
| 148 | 13 | |
| 165 | 7 | |
| 210 | 11 | I210T, |
| 204 | 0 | c.611+3_611+4dupAA, A204V, c.611+1G>A, A204T, |
| 162 | 10 | Y162H, Y162C, |
| 203 | 5 | |
| 208 | 6 | E208K, |
| 168 | 9 | |
| 202 | 6 | I202T, |
| 141 | 14 | I141V, I141N, |
| 167 | 12 | |
| 161 | 9 | E161Q, E161K, |
| 201 | 5 | |
| 219 | 9 | R219C, R219H, c.656_657insATTCA, p.R219HfsX11, |
| 225 | 11 | R225W, R225Q, |
| 151 | 15 | |
| 218 | 7 | |
| 207 | 5 | |
| 212 | 12 | L212Q, L212P, |
| 215 | 13 | p.L215CfsX10, |
| 200 | 7 | |
| 140 | 14 | |
| 220 | 11 | T220I, |