SCN5A Variant c.4376_4379delTCTT
Summary of observed carriers, functional annotations, and structural context for SCN5A c.4376_4379delTCTT. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
19%
1/11 effective observations
Estimated BrS1 penetrance
49%
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 (%) |
|---|---|---|---|---|---|
| NA | NA | NA | None | 64 | 29 |
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 | 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) |
|---|---|---|---|---|---|---|
| 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 | 14 | I891N, I891T, |
| 888 | 14 | |
| 939 | 15 | L939F, |
| 896 | 7 | C896S, C896S, |
| 937 | 12 | |
| 895 | 8 | L895F, |
| 1417 | 11 | |
| 1765 | 15 | |
| 839 | 11 | L839P, |
| 842 | 10 | |
| 894 | 13 | I894M, |
| 1457 | 6 | |
| 1453 | 9 | |
| 1455 | 5 | |
| 1449 | 14 | Y1449S, Y1449C, |
| 1452 | 10 | |
| 1461 | 8 | T1461S, T1461S, |
| 926 | 11 | |
| 409 | 14 | L409V, L409P, |
| 1344 | 13 | F1344L, F1344S, F1344L, F1344L, |
| 928 | 13 | L928P, |
| 1450 | 12 | |
| 925 | 15 | I925F, |
| 1451 | 9 | V1451L, V1451D, |
| 934 | 7 | |
| 1458 | 4 | S1458Y, |
| 933 | 11 | |
| 935 | 9 | L935P, |
| 897 | 11 | G897R, G897R, G897E, |
| 1348 | 14 | F1348L, F1348L, F1348L, |
| 1464 | 11 | c.4389_4396delCCTCTTTA, L1464P, |
| 927 | 10 | N927S, N927K, N927K, |
| 1466 | 13 | c.4396_4397insG, |
| 845 | 13 | c.2533delG, |
| 1418 | 9 | |
| 892 | 9 | F892I, |
| 849 | 14 | |
| 1341 | 13 | |
| 898 | 14 | |
| 893 | 14 | R893C, R893H, |
| 922 | 15 | V922I, |
| 1462 | 8 | |
| 938 | 11 | |
| 1412 | 14 | L1412F, |
| 840 | 13 | |
| 889 | 15 | |
| 942 | 15 | |
| 843 | 10 | T843A, |
| 1456 | 8 | |
| 930 | 10 | c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T, |
| 1459 | 0 | c.4376_4379delTCTT, |
| 1460 | 7 | F1460L, F1460L, F1460L, |
| 1454 | 6 | |
| 929 | 13 | |
| 1448 | 14 | I1448L, I1448T, |
| 1421 | 13 | |
| 847 | 12 | |
| 1345 | 13 | W1345C, W1345C, |
| 846 | 9 | L846R, |
| 936 | 13 | |
| 1416 | 9 | c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G, |
| 838 | 15 | |
| 1465 | 13 | p.F1465_L1480dup, |
| 1760 | 14 | |
| 1467 | 14 | |
| 1761 | 14 | c.5280delG, L1761F, L1761H |
| 923 | 14 | |
| 1415 | 11 | |
| 844 | 14 | L844RfsX3, |
| 850 | 13 | V850M, c.2549_2550insTG, |
| 932 | 10 | |
| 832 | 14 | |
| 835 | 15 | S835A, S835L, |
| 1419 | 15 | K1419E, |
| 931 | 6 | |
| 1463 | 7 | N1463Y, |
| 1413 | 14 |