SCN5A Variant E444fsX14
Summary of observed carriers, functional annotations, and structural context for SCN5A E444fsX14. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/11 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 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 47 | 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 |
|---|---|---|---|---|---|---|---|
| 29574140 | 2018 | 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) |
|---|---|---|---|---|---|---|
| 29574140 | 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 |
|---|---|---|
| 429 | 15 | E429K, p.E429del, |
| 430 | 14 | K430E, |
| 431 | 14 | |
| 432 | 13 | |
| 433 | 13 | R433H, R433S, R433C, |
| 434 | 12 | |
| 435 | 11 | |
| 436 | 11 | |
| 437 | 10 | A437V, |
| 438 | 9 | M438T, M438L, M438L, |
| 439 | 8 | E439V, E439K, |
| 440 | 8 | |
| 441 | 7 | L441F, |
| 442 | 5 | |
| 443 | 4 | |
| 444 | 0 | E444fsX14, |
| 445 | 4 | H445Q, H445Y, H445D, H445Q, |
| 446 | 5 | E446K, |
| 447 | 7 | c.1339-24G>A, A447G, A447S, c.1338+2T>A, |
| 448 | 8 | |
| 449 | 8 | Y449C, T449A, |
| 450 | 9 | |
| 451 | 10 | |
| 452 | 11 | G452D, |
| 453 | 11 | V453M, |
| 454 | 12 | |
| 455 | 13 | |
| 456 | 13 | V456M, |
| 457 | 14 | |
| 458 | 14 | R458H, R458C, p.R458VfsX12, |
| 459 | 15 | S459G, |