SCN5A Variant I1448T
Summary of observed carriers, functional annotations, and structural context for SCN5A I1448T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
1%
0/11 effective observations
Estimated BrS1 penetrance
46%
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 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -3.44 | 0.666 | -2.64 | 0.931 | 55 | 3 |
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 |
|---|---|---|---|---|---|---|---|
| 20129283 | 2010 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 1 | 0 | 0 | 1 | – | |
| Variant features alone | – | 15 | 11 | 0 | 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) |
|---|---|---|---|---|---|---|
| 20129283 | 2010 |
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 |
|---|---|---|
| 891 | 15 | I891N, I891T, |
| 888 | 9 | |
| 1355 | 12 | |
| 890 | 15 | I890T, |
| 896 | 15 | C896S, C896S, |
| 895 | 15 | L895F, |
| 1352 | 13 | |
| 1445 | 8 | Y1445H, |
| 1457 | 14 | |
| 1453 | 10 | |
| 1455 | 10 | |
| 1447 | 4 | |
| 1444 | 9 | L1444I, |
| 1351 | 11 | M1351V, M1351R, |
| 1449 | 6 | Y1449S, Y1449C, |
| 1452 | 6 | |
| 1429 | 11 | |
| 806 | 14 | V806M, |
| 1450 | 7 | |
| 887 | 14 | |
| 1451 | 5 | V1451L, V1451D, |
| 886 | 13 | H886P, H886Q, H886Q, |
| 1458 | 15 | S1458Y, |
| 851 | 15 | c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L, |
| 1348 | 11 | F1348L, F1348L, F1348L, |
| 1431 | 15 | S1431C, |
| 1422 | 15 | M1422R, |
| 892 | 10 | F892I, |
| 1356 | 13 | c.4066_4068delTT, |
| 1412 | 14 | L1412F, |
| 889 | 10 | |
| 843 | 14 | T843A, |
| 1456 | 12 | |
| 1459 | 14 | c.4376_4379delTCTT |
| 1425 | 10 | |
| 1454 | 10 | |
| 1446 | 6 | |
| 1424 | 15 | I1424V, |
| 1448 | 0 | I1448L, I1448T, |
| 884 | 12 | |
| 809 | 14 | |
| 1421 | 14 | |
| 885 | 9 | |
| 847 | 13 | |
| 1443 | 12 | N1443S, |
| 846 | 15 | L846R, |
| 879 | 15 | W879R, W879R, |
| 883 | 15 | |
| 1415 | 13 | |
| 1428 | 12 | A1428S, A1428V, |
| 850 | 14 | V850M, c.2549_2550insTG, |