SCN5A Variant L399M
Summary of observed carriers, functional annotations, and structural context for SCN5A L399M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
22%
1/10 effective observations
Estimated BrS1 penetrance
20%
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 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | 0.772 | 23 | 27 |
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 | 12 | 1 | 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 |
|---|---|---|
| 403 | 6 | |
| 1659 | 14 | |
| 404 | 9 | L404V, L404Q, |
| 396 | 7 | V396L, V396A, |
| 1624 | 15 | V1624I, |
| 1653 | 12 | |
| 391 | 11 | |
| 1771 | 12 | I1771T |
| 401 | 8 | S401P, |
| 1634 | 14 | L1634P, |
| 1764 | 14 | c.5290delG, V1764F, |
| 371 | 13 | Q371E, |
| 1650 | 10 | L1650F, |
| 260 | 9 | |
| 366 | 15 | |
| 1656 | 13 | |
| 365 | 12 | |
| 369 | 10 | M369K, |
| 1767 | 10 | Y1767C, |
| 1660 | 12 | I1660V, I1660S, |
| 1654 | 9 | |
| 402 | 7 | F402L, F402L, F402L, |
| 1630 | 15 | I1630V, I1630R, |
| 1649 | 14 | A1649V, |
| 1768 | 14 | I1768V, |
| 267 | 13 | |
| 262 | 14 | S262G, |
| 256 | 13 | |
| 399 | 0 | |
| 397 | 7 | I397V, I397F, I397T, |
| 405 | 12 | |
| 1657 | 9 | |
| 261 | 12 | |
| 1662 | 14 | |
| 1709 | 14 | p.T1709del, T1709R, T1709M, |
| 1628 | 13 | |
| 392 | 10 | |
| 395 | 5 | |
| 393 | 11 | |
| 390 | 13 | |
| 394 | 8 | |
| 1770 | 14 | I1770V, |
| 264 | 9 | |
| 1651 | 12 | |
| 1708 | 15 | T1708I, |
| 259 | 13 | |
| 265 | 14 | A265V, |
| 374 | 14 | W374G, |
| 1705 | 14 | |
| 407 | 13 | |
| 263 | 11 | V263I, |
| 370 | 14 | T370M, |
| 1661 | 11 | G1661R, G1661R, G1661E, |
| 1655 | 12 | |
| 1631 | 13 | G1631D, |
| 406 | 12 | N406S, N406K, N406K, |
| 368 | 11 | |
| 398 | 5 | |
| 1647 | 13 | |
| 257 | 13 | |
| 400 | 5 | G400R, G400R, G400E, G400A, |
| 1646 | 15 | |
| 1664 | 13 | |
| 1658 | 9 |