SCN5A Variant M440I
Summary of observed carriers, functional annotations, and structural context for SCN5A M440I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/10 effective observations
Estimated BrS1 penetrance
24%
2/10 effective observations
Total carriers
0
0 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 | 0.316 | 33 | 1 |
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 |
|---|---|---|---|---|---|---|---|
| Literature, cohort, and gnomAD | – | 0 | 0 | 0 | 0 | – | |
| Variant features alone | – | 15 | 13 | 0 | 2 | – | – |
Totals may differ from individual publications due to duplicate patients removed during curation.
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 |
|---|---|---|
| 425 | 15 | A425T, A425P, |
| 426 | 14 | |
| 427 | 14 | |
| 428 | 13 | E428K, |
| 429 | 13 | p.E429del, E429K, |
| 430 | 12 | K430E, |
| 431 | 11 | |
| 432 | 11 | |
| 433 | 10 | R433C, R433S, R433H, |
| 434 | 9 | |
| 435 | 8 | |
| 436 | 8 | |
| 437 | 7 | A437V |
| 438 | 5 | M438L, M438T, M438L, |
| 439 | 4 | E439K, E439V, |
| 440 | 0 | |
| 441 | 4 | L441F, |
| 442 | 5 | |
| 443 | 7 | |
| 444 | 8 | E444fsX14, |
| 445 | 8 | H445Q, H445Q, H445D, H445Y, |
| 446 | 9 | E446K, |
| 447 | 10 | A447G, c.1338+2T>A, c.1339-24G>A, A447S, |
| 448 | 11 | |
| 449 | 11 | T449A, Y449C, |
| 450 | 12 | |
| 451 | 13 | |
| 452 | 13 | G452D, |
| 453 | 14 | V453M, |
| 454 | 14 | |
| 455 | 15 |