SCN5A Variant L404Q
Summary of observed carriers, functional annotations, and structural context for SCN5A L404Q. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
46%
2/11 effective observations
Estimated BrS1 penetrance
11%
1/11 effective observations
Total carriers
1
0 BrS1 · 1 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.88 | 1 | -5.17 | 0.984 | 5 | 49 |
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 |
|---|---|---|---|---|---|---|---|
| 15840476 | 2005 | 1 | 1 | 0 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 1 | 0 | – | |
| Variant features alone | – | 15 | 13 | 1 | 1 | – | – |
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) |
|---|---|---|---|---|---|---|
| 15840476 | 2005 |
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 | |
| 1643 | 12 | I1643L, |
| 404 | 0 | L404V, L404Q, |
| 249 | 15 | K249X, |
| 396 | 10 | V396L, V396A, |
| 247 | 15 | V247L, V247L, |
| 1653 | 13 | |
| 254 | 9 | |
| 1771 | 10 | I1771T, |
| 401 | 6 | S401P, |
| 1634 | 15 | L1634P, |
| 1764 | 14 | c.5290delG, V1764F, |
| 371 | 11 | Q371E, |
| 250 | 10 | |
| 409 | 10 | L409V, L409P, |
| 928 | 10 | L928P, |
| 1650 | 9 | L1650F, |
| 260 | 8 | |
| 366 | 10 | |
| 365 | 12 | |
| 258 | 11 | V258A, |
| 246 | 15 | |
| 412 | 13 | V412D, |
| 924 | 12 | V924I, |
| 927 | 13 | N927S, N927K, N927K, |
| 369 | 6 | M369K, |
| 1767 | 11 | Y1767C, |
| 1654 | 13 | |
| 1769 | 14 | |
| 402 | 8 | F402L, F402L, F402L, |
| 1649 | 12 | A1649V, |
| 1768 | 11 | I1768V, |
| 1774 | 15 | N1774D, c.5321_5324dupACTT, |
| 262 | 13 | S262G, |
| 256 | 8 | |
| 399 | 9 | |
| 397 | 10 | I397V, I397F, I397T, |
| 405 | 5 | |
| 1657 | 13 | |
| 362 | 14 | |
| 261 | 9 | |
| 920 | 15 | |
| 255 | 11 | |
| 1772 | 12 | L1772V, |
| 395 | 13 | |
| 251 | 13 | |
| 410 | 10 | A410V, |
| 1770 | 14 | I1770V, |
| 264 | 12 | |
| 929 | 13 | |
| 1651 | 14 | |
| 259 | 11 | |
| 413 | 15 | A413T, A413E, |
| 408 | 6 | |
| 253 | 8 | |
| 407 | 5 | |
| 367 | 15 | R367C, R367H, R367L, |
| 263 | 13 | V263I, |
| 1775 | 12 | F1775V, p.F1775LfsX15 |
| 370 | 10 | T370M, |
| 1642 | 14 | G1642E, |
| 923 | 13 | |
| 406 | 7 | N406S, N406K, N406K, |
| 368 | 12 | |
| 252 | 13 | |
| 411 | 11 | V411M, |
| 932 | 12 | |
| 398 | 11 | |
| 1647 | 11 | |
| 257 | 6 | |
| 400 | 5 | G400R, G400R, G400E, G400A, |
| 1646 | 10 |