SCN5A Variant c.486delC
Summary of observed carriers, functional annotations, and structural context for SCN5A c.486delC. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/11 effective observations
Estimated BrS1 penetrance
45%
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 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 57 | 0 |
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 | 12 | 0 | 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 |
|---|---|---|
| 147 | 11 | |
| 164 | 5 | F164L, |
| 170 | 11 | F170I, |
| 171 | 13 | |
| 143 | 11 | |
| 137 | 12 | I137V, |
| 142 | 15 | |
| 156 | 15 | W156R, W156X, |
| 158 | 10 | K158T, |
| 163 | 0 | c.486delC, |
| 169 | 10 | |
| 222 | 13 | R222L, R222X, R222Q, |
| 157 | 10 | T157I, |
| 160 | 5 | p.V160fs |
| 205 | 13 | Y205X, c.612-2A>G, |
| 166 | 5 | A166T, |
| 144 | 11 | |
| 172 | 15 | |
| 139 | 13 | p.I137_C139dup, |
| 148 | 14 | |
| 165 | 6 | |
| 204 | 12 | c.611+1G>A, c.611+3_611+4dupAA, A204V, A204T, |
| 162 | 6 | Y162C, Y162H, |
| 146 | 15 | V146A, V146M, |
| 208 | 11 | E208K, |
| 136 | 13 | L136P, |
| 168 | 9 | |
| 141 | 13 | I141V, I141N, |
| 167 | 6 | |
| 161 | 7 | E161Q, E161K, |
| 201 | 13 | |
| 225 | 14 | R225Q, R225W, |
| 151 | 15 | |
| 159 | 7 | Y159X, Y159C, |
| 207 | 14 | |
| 145 | 15 | |
| 140 | 9 |