SCN5A Variant I1350T
Summary of observed carriers, functional annotations, and structural context for SCN5A I1350T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/11 effective observations
Estimated BrS1 penetrance
42%
4/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -4.86 | 0.994 | -3.23 | 0.959 | 50 | 0 |
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 |
|---|---|---|---|---|---|---|---|
| 12845244 | 2003 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 12 | 0 | 3 | – | – |
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) |
|---|---|---|---|---|---|---|
| 12845244 | 2003 |
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 |
|---|---|---|
| 1355 | 10 | |
| 1403 | 12 | |
| 1357 | 10 | A1357V, |
| 811 | 9 | R811G, c.2435_2436+3delTGGTAinsCGCCT, R811H, |
| 733 | 11 | F733L, |
| 741 | 14 | p.M741_T742delinsI , |
| 808 | 10 | R808H, R808P, R808C, |
| 1352 | 6 | |
| 1406 | 11 | G1406E, G1406R, |
| 1453 | 12 | |
| 1351 | 6 | M1351R, M1351V, |
| 739 | 14 | |
| 1449 | 11 | Y1449C, Y1449S, |
| 1452 | 14 | |
| 812 | 7 | L812Q, |
| 1350 | 0 | I1350T, I1350L, |
| 1344 | 12 | F1344S, F1344L, |
| 731 | 8 | T731I, |
| 806 | 14 | V806M, |
| 1450 | 14 | |
| 818 | 14 | |
| 1411 | 13 | |
| 1353 | 5 | V1353M, |
| 1407 | 11 | |
| 737 | 7 | |
| 1410 | 14 | |
| 1358 | 14 | G1358R, G1358W, |
| 1348 | 8 | F1348L, |
| 1404 | 10 | |
| 1349 | 4 | |
| 749 | 13 | |
| 1346 | 6 | L1346P, L1346I, |
| 805 | 14 | S805L, |
| 1359 | 14 | K1359M, K1359N, |
| 1341 | 15 | |
| 1356 | 11 | c.4066_4068delTT, |
| 1434 | 15 | c.4300-2A>T, c.4299+1G>T, Y1434X, c.4299+1delG, c.4299G>A, c.4300-1G>A, c.4299delG, c.4299+28C>T, c.4299_4300insG, c.4299+2T>A, |
| 728 | 14 | V728I, |
| 1412 | 11 | L1412F, |
| 810 | 12 | |
| 727 | 14 | |
| 1408 | 9 | G1408R, |
| 735 | 6 | A735T, A735V, A735E, |
| 732 | 10 | |
| 734 | 6 | c.2201dupT, M734V, |
| 814 | 12 | R814Q, |
| 807 | 15 | |
| 816 | 12 | F816L, F816Y, |
| 1401 | 13 | |
| 813 | 12 | c.2436+12G>A, c.2437-5C>A, |
| 1354 | 6 | |
| 738 | 12 | |
| 1405 | 7 | V1405M, V1405L, |
| 809 | 9 | |
| 1409 | 11 | Y1409X, Y1409C, |
| 815 | 10 | |
| 1343 | 11 | |
| 1345 | 11 | W1345C, |
| 1342 | 12 | |
| 736 | 9 | L736P, |
| 730 | 11 | N730K, |
| 753 | 13 | |
| 1347 | 6 | |
| 729 | 14 | p.L729del, |
| 1402 | 10 | |
| 1413 | 15 |