SCN5A Variant K430E
Summary of observed carriers, functional annotations, and structural context for SCN5A K430E. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
10%
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 (%) |
|---|---|---|---|---|---|
| -3.84 | 0.997 | 2.26 | 0.768 | 51 | 7 |
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 |
|---|---|---|---|---|---|---|---|
| 29325976 | 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) |
|---|---|---|---|---|---|---|
| 29325976 | 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 |
|---|---|---|
| 415 | 15 | A415T, |
| 416 | 14 | Y416C, |
| 417 | 14 | |
| 418 | 13 | E418K, |
| 419 | 13 | Q419X, |
| 420 | 12 | |
| 421 | 11 | |
| 422 | 11 | |
| 423 | 10 | |
| 424 | 9 | I424M, |
| 425 | 8 | A425T, A425P, |
| 426 | 8 | |
| 427 | 7 | |
| 428 | 5 | E428K, |
| 429 | 4 | E429K, p.E429del, |
| 430 | 0 | K430E, |
| 431 | 4 | |
| 432 | 5 | |
| 433 | 7 | R433S, R433C, R433H, |
| 434 | 8 | |
| 435 | 8 | |
| 436 | 9 | |
| 437 | 10 | A437V, |
| 438 | 11 | M438L, M438L, M438T, |
| 439 | 11 | E439K, E439V, |
| 440 | 12 | |
| 441 | 13 | L441F, |
| 442 | 13 | |
| 443 | 14 | |
| 444 | 14 | E444fsX14, |
| 445 | 15 | H445D, H445Y, H445Q, H445Q |