SCN5A Variant F1344L
Summary of observed carriers, functional annotations, and structural context for SCN5A F1344L. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
7%
0/11 effective observations
Estimated BrS1 penetrance
62%
6/11 effective observations
Total carriers
1
1 BrS1 · 0 LQT3 · 0 unaffected
Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
|---|---|---|---|---|---|
| -5.85 | 0.998 | 2.06 | 0.885 | 92 | 1 |
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 | 10 | 0 | 5 | – | – |
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 |
|---|---|---|
| 1352 | 15 | |
| 821 | 14 | |
| 1340 | 5 | V1340I, |
| 1457 | 8 | |
| 1453 | 9 | |
| 1455 | 11 | |
| 1339 | 9 | L1339F, p.L1339del, |
| 1351 | 11 | M1351V, M1351R, |
| 1449 | 13 | Y1449C, Y1449S, |
| 1452 | 12 | |
| 1461 | 7 | T1461S, T1461S, |
| 812 | 11 | L812Q, |
| 1350 | 12 | I1350T, I1350L, |
| 1344 | 0 | F1344S, F1344L, F1344L, F1344L, |
| 731 | 13 | T731I, |
| 1450 | 15 | |
| 819 | 10 | |
| 826 | 13 | N826D, |
| 818 | 11 | |
| 1451 | 15 | V1451D, V1451L, |
| 825 | 9 | |
| 1458 | 12 | S1458Y, |
| 1348 | 7 | F1348L, F1348L, F1348L, |
| 1464 | 11 | c.4389_4396delCCTCTTTA, L1464P, |
| 1349 | 10 | |
| 822 | 12 | W822C, W822X, W822C, |
| 1346 | 7 | L1346I, L1346P, |
| 833 | 15 | G833R, G833R, |
| 1341 | 6 | |
| 831 | 14 | |
| 1462 | 12 | |
| 938 | 15 | |
| 1412 | 12 | L1412F, |
| 823 | 15 | P823T, |
| 1408 | 14 | G1408R, G1408R, |
| 942 | 14 | |
| 1456 | 7 | |
| 1459 | 13 | c.4376_4379delTCTT, |
| 734 | 15 | c.2201dupT, M734V, |
| 827 | 13 | |
| 1460 | 9 | F1460L, F1460L, F1460L, |
| 816 | 8 | F816L, F816L, F816L, F816Y, |
| 813 | 13 | c.2436+12G>A, c.2437-5C>A, |
| 1454 | 12 | |
| 1338 | 11 | L1338V, |
| 817 | 14 | K817E, |
| 1405 | 14 | V1405M, V1405L, V1405L, |
| 1409 | 12 | Y1409X, Y1409C, |
| 815 | 9 | |
| 1343 | 5 | |
| 1345 | 6 | W1345C, W1345C, |
| 1337 | 10 | |
| 1342 | 7 | |
| 1416 | 13 | A1416E, A1416G, c.4245+2T>A, c.4245+1G>C, c.4245+1G>A, |
| 1465 | 13 | p.F1465_L1480dup, |
| 1347 | 6 | |
| 1336 | 13 | |
| 1415 | 15 | |
| 824 | 12 | |
| 829 | 10 | |
| 832 | 11 | |
| 828 | 9 | L828V, |
| 1463 | 14 | N1463Y, |
| 1413 | 13 |