SCN5A Variant c.704-1G>C
Summary of observed carriers, functional annotations, and structural context for SCN5A c.704-1G>C. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
12%
0/11 effective observations
Estimated BrS1 penetrance
31%
3/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 2 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 | 29 | 17 |
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 |
|---|---|---|---|---|---|---|---|
| 22885917 | 2012 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 13 | 0 | 2 | – | – |
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) |
|---|---|---|---|---|---|---|
| 22885917 | 2012 |
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 |
|---|---|---|
| 848 | 14 | I848F |
| 937 | 13 | |
| 839 | 12 | L839P, |
| 842 | 10 | |
| 240 | 9 | V240M, |
| 231 | 9 | c.692_693delCA, |
| 193 | 15 | W193R, W193R, W193X, |
| 237 | 6 | |
| 228 | 14 | K228R, |
| 836 | 12 | V836M, |
| 234 | 4 | P234S, |
| 229 | 13 | |
| 933 | 14 | |
| 845 | 11 | c.2533delG, |
| 232 | 9 | V232I, V232F, |
| 244 | 14 | |
| 420 | 11 | |
| 241 | 10 | |
| 235 | 0 | c.703+1G>A, G235R, G235R, c.704-1G>C, |
| 840 | 10 | |
| 843 | 13 | T843A, |
| 419 | 10 | Q419X, |
| 423 | 10 | |
| 834 | 15 | N834D, |
| 837 | 8 | |
| 239 | 7 | I239V, I239V , |
| 230 | 10 | I230V, I230T, I230M, |
| 242 | 11 | A242D, |
| 416 | 12 | Y416C, |
| 841 | 6 | p.N841TfsX2, N841K, N841K, |
| 236 | 4 | |
| 238 | 5 | |
| 233 | 6 | |
| 838 | 8 | |
| 422 | 13 | |
| 844 | 11 | L844RfsX3, |
| 243 | 13 | |
| 835 | 12 | S835A, S835L, |