SCN5A Variant M394I
Summary of observed carriers, functional annotations, and structural context for SCN5A M394I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
20%
1/10 effective observations
Estimated BrS1 penetrance
34%
3/10 effective observations
Total carriers
0
0 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | 0.477 | 50 | 26 |
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 | 11 | 1 | 3 | – | – |
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 |
|---|---|---|
| 403 | 12 | |
| 271 | 14 | L271V, |
| 1702 | 11 | |
| 1659 | 15 | |
| 387 | 12 | |
| 396 | 7 | V396L, V396A, |
| 391 | 5 | |
| 388 | 11 | I388S, |
| 1698 | 14 | A1698T, |
| 401 | 11 | S401P, |
| 1764 | 14 | c.5290delG, V1764F, |
| 1666 | 15 | |
| 371 | 12 | Q371E, |
| 1711 | 15 | c.5131delG, |
| 1707 | 14 | |
| 365 | 13 | |
| 1704 | 12 | L1704H, |
| 1706 | 12 | Q1706H, |
| 1668 | 11 | M1668T, |
| 386 | 13 | G386E, G386R, |
| 369 | 13 | M369K, |
| 1767 | 13 | Y1767C, |
| 1660 | 13 | I1660V, I1660S, |
| 378 | 10 | |
| 1654 | 15 | |
| 402 | 10 | F402L, |
| 1665 | 10 | |
| 267 | 13 | |
| 1703 | 14 | |
| 1663 | 14 | |
| 399 | 8 | |
| 272 | 15 | |
| 397 | 7 | I397F, I397T, I397V |
| 1657 | 13 | |
| 1759 | 15 | S1759C, |
| 1662 | 12 | |
| 1709 | 11 | T1709R, p.T1709del, T1709M, |
| 1701 | 10 | M1701I, |
| 392 | 7 | |
| 389 | 11 | Y389X, Y389H, |
| 395 | 5 | |
| 393 | 6 | |
| 390 | 6 | |
| 394 | 0 | |
| 264 | 11 | |
| 1708 | 11 | T1708I, |
| 382 | 12 | |
| 374 | 11 | W374G, |
| 1705 | 7 | |
| 1700 | 14 | |
| 1661 | 10 | G1661E, G1661R, |
| 381 | 13 | c.1140+1G>A, c.1141-3C>A, |
| 368 | 11 | |
| 268 | 15 | G268S, |
| 377 | 14 | |
| 398 | 6 | |
| 400 | 10 | G400E, G400A, G400R, |
| 1667 | 15 | V1667I, |
| 1664 | 10 | |
| 1658 | 12 |