SCN5A Variant A1416G
Summary of observed carriers, functional annotations, and structural context for SCN5A A1416G. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
22%
1/11 effective observations
Estimated BrS1 penetrance
47%
5/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 4 individuals for Brugada syndrome and 1 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.82 | 0.998 | -1.91 | 0.937 | 60 | 36 |
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 |
|---|---|---|---|---|---|---|---|
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 10 | 1 | 4 | – | – |
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) |
|---|---|---|---|---|---|---|
| 29325976 | 2018 |
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 |
|---|---|---|
| 896 | 9 | C896S, C896S, |
| 895 | 13 | L895F, |
| 1417 | 4 | |
| 1765 | 15 | |
| 1406 | 15 | G1406R, G1406R, G1406E, |
| 1340 | 15 | V1340I, |
| 1457 | 6 | |
| 1453 | 7 | |
| 1455 | 10 | |
| 1757 | 13 | |
| 1449 | 12 | Y1449S, Y1449C, |
| 1452 | 12 | |
| 1756 | 11 | I1756V, |
| 1461 | 9 | T1461S, T1461S, |
| 1711 | 13 | c.5131delG, |
| 1344 | 13 | F1344L, F1344S, F1344L, F1344L, |
| 1450 | 10 | |
| 1411 | 9 | |
| 1451 | 11 | V1451L, V1451D, |
| 1407 | 14 | |
| 934 | 15 | |
| 1458 | 5 | S1458Y, |
| 1410 | 11 | |
| 1714 | 12 | D1714G, |
| 897 | 12 | G897R, G897R, G897E, |
| 1348 | 11 | F1348L, F1348L, F1348L, |
| 1464 | 13 | c.4389_4396delCCTCTTTA, L1464P, |
| 1423 | 14 | D1423H, |
| 927 | 15 | N927S, N927K, N927K, |
| 1349 | 13 | |
| 1753 | 13 | T1753A, |
| 1422 | 12 | M1422R, |
| 1346 | 14 | L1346I, L1346P, |
| 1418 | 5 | |
| 892 | 12 | F892I, |
| 1712 | 13 | G1712S, G1712C, |
| 1341 | 11 | |
| 898 | 12 | |
| 893 | 13 | R893C, R893H, |
| 1462 | 7 | |
| 1412 | 7 | L1412F, |
| 1759 | 15 | S1759C, |
| 1408 | 12 | G1408R, G1408R, |
| 1709 | 14 | p.T1709del, T1709R, T1709M, |
| 1420 | 10 | G1420R, G1420D, G1420V, G1420P, |
| 1456 | 11 | |
| 1459 | 9 | c.4376_4379delTCTT, |
| 1460 | 12 | F1460L, F1460L, F1460L, |
| 1425 | 12 | |
| 1713 | 10 | |
| 1454 | 6 | |
| 1338 | 14 | L1338V, |
| 1424 | 11 | I1424V, |
| 1409 | 10 | Y1409C, Y1409X, |
| 1400 | 13 | V1400I, |
| 1421 | 8 | |
| 1345 | 8 | W1345C, W1345C, |
| 1337 | 15 | |
| 1717 | 15 | L1717P, |
| 1342 | 13 | |
| 1416 | 0 | c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G, |
| 1465 | 12 | p.F1465_L1480dup, |
| 1760 | 10 | |
| 1752 | 15 | |
| 1761 | 11 | c.5280delG, L1761F, L1761H |
| 1347 | 15 | |
| 1710 | 10 | S1710L, |
| 1415 | 4 | |
| 1419 | 8 | K1419E, |
| 1414 | 7 | Q1414H, Q1414H, |
| 931 | 14 | |
| 1402 | 14 | |
| 1463 | 10 | N1463Y, |
| 1413 | 6 |