SCN5A Variant Q371E
Summary of observed carriers, functional annotations, and structural context for SCN5A Q371E. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
39%
3/14 effective observations
Estimated BrS1 penetrance
13%
1/14 effective observations
Total carriers
4
0 BrS1 · 2 LQT3 · 2 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 (%) |
|---|---|---|---|---|---|
| -2.94 | 0.895 | -2.67 | 0.941 | 19 | 45 |
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 |
|---|---|---|---|---|---|---|---|
| 28011106 | 2017 | 4 | 2 | 0 | 0 | DCM | |
| Literature, cohort, and gnomAD | – | 4 | 2 | 2 | 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) |
|---|---|---|---|---|---|---|
| 28011106 | 2017 |
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 | 13 | |
| 364 | 11 | |
| 363 | 14 | |
| 896 | 13 | C896S, C896S, |
| 404 | 11 | L404V, L404Q, |
| 895 | 15 | L895F, |
| 1417 | 12 | |
| 1765 | 13 | |
| 396 | 9 | V396L, V396A, |
| 894 | 14 | I894M, |
| 372 | 6 | |
| 401 | 6 | S401P, |
| 1764 | 11 | c.5290delG, V1764F, |
| 371 | 0 | Q371E, |
| 409 | 15 | L409V, L409P, |
| 1711 | 8 | c.5131delG, |
| 928 | 12 | L928P, |
| 366 | 10 | |
| 1707 | 12 | |
| 365 | 11 | |
| 1704 | 15 | L1704H, |
| 1706 | 10 | Q1706H, Q1706H, |
| 376 | 13 | R376C, R376H, |
| 897 | 9 | G897R, G897R, G897E, |
| 924 | 15 | V924I, |
| 927 | 12 | N927S, N927K, N927K, |
| 369 | 7 | M369K, |
| 1767 | 13 | Y1767C, |
| 378 | 12 | |
| 1418 | 12 | |
| 402 | 8 | F402L, F402L, F402L, |
| 373 | 8 | |
| 1768 | 13 | I1768V |
| 1712 | 12 | G1712S, G1712C, |
| 379 | 15 | |
| 898 | 11 | |
| 893 | 14 | R893C, R893H, |
| 399 | 13 | |
| 397 | 6 | I397V, I397F, I397T, |
| 405 | 9 | |
| 1759 | 13 | S1759C, |
| 261 | 14 | |
| 920 | 15 | |
| 1709 | 6 | p.T1709del, T1709R, T1709M, |
| 900 | 12 | |
| 392 | 13 | |
| 395 | 13 | |
| 393 | 10 | |
| 1713 | 13 | |
| 394 | 12 | |
| 264 | 14 | |
| 1708 | 10 | T1708I, |
| 408 | 14 | |
| 374 | 6 | W374G, |
| 1705 | 12 | |
| 407 | 15 | |
| 367 | 8 | R367C, R367H, R367L, |
| 1763 | 15 | V1763M, V1763L, V1763L, |
| 1760 | 11 | |
| 370 | 5 | T370M, |
| 1761 | 15 | c.5280delG, L1761F, L1761H, |
| 923 | 12 | |
| 375 | 10 | |
| 406 | 11 | N406S, N406K, N406K, |
| 368 | 6 | |
| 899 | 10 | |
| 1710 | 8 | S1710L, |
| 377 | 11 | |
| 932 | 14 | |
| 398 | 11 | |
| 257 | 15 | |
| 400 | 9 | G400R, G400R, G400E, G400A, |
| 1419 | 11 | K1419E, |
| 931 | 15 | |
| 1664 | 14 |