SCN5A Variant E1548K
Summary of observed carriers, functional annotations, and structural context for SCN5A E1548K. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
3%
0/14 effective observations
Estimated BrS1 penetrance
51%
7/14 effective observations
Total carriers
4
3 BrS1 · 0 LQT3 · 1 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 (%) |
|---|---|---|---|---|---|
| -3.63 | 0.902 | 2.97 | 0.958 | 64 | 2 |
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 |
|---|---|---|---|---|---|---|---|
| 17404158 | 2007 | 1 | 0 | 1 | 0 | ||
| 26921764 | 2016 | 1 | 0 | 1 | 0 | ||
| 20129283 | 2010 | 3 | 0 | 3 | 0 | ||
| 29325976 | 2018 | 1 | 0 | 1 | 0 | ||
| Literature, cohort, and gnomAD | – | 4 | 1 | 0 | 3 | – | |
| 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.
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 |
|---|---|---|
| 277 | 15 | |
| 271 | 12 | L271V, |
| 266 | 9 | L266H, |
| 1544 | 7 | T1544P, |
| 270 | 7 | Q270K, |
| 360 | 15 | |
| 1627 | 13 | |
| 1567 | 14 | F1567L, F1567L, F1567L, |
| 1624 | 14 | V1624I, |
| 1552 | 8 | Q1552R, Q1552L, |
| 355 | 12 | F355I, F355C, |
| 1549 | 5 | |
| 1556 | 8 | |
| 356 | 9 | D356N, |
| 1543 | 10 | V1543L, V1543L, V1543A, |
| 1558 | 12 | |
| 1542 | 11 | |
| 1557 | 8 | I1557V, |
| 361 | 12 | |
| 1562 | 14 | |
| 1564 | 11 | |
| 354 | 14 | |
| 1546 | 7 | M1546T, |
| 1545 | 6 | |
| 1626 | 12 | R1626C, R1626H, R1626P, R1626L |
| 267 | 12 | |
| 1550 | 9 | |
| 1560 | 7 | L1560F, L1560F, |
| 262 | 14 | S262G, |
| 357 | 9 | |
| 272 | 13 | |
| 274 | 12 | G274C, |
| 273 | 7 | |
| 1559 | 11 | I1559V, |
| 1553 | 10 | S1553R, S1553R, S1553R, |
| 269 | 7 | |
| 1620 | 14 | T1620K, T1620M, |
| 275 | 14 | N275K, N275K, |
| 1548 | 0 | E1548K, G1548K, |
| 1555 | 13 | E1555K, |
| 265 | 12 | A265V, |
| 1619 | 13 | P1619Q, P1619L, c.4856delC, |
| 358 | 10 | |
| 1551 | 9 | D1551N, D1551Y, |
| 263 | 15 | V263I, |
| 359 | 13 | A359T, p.A359PfsX12, |
| 1547 | 5 | V1547L, V1547L, |
| 1563 | 11 | |
| 1541 | 11 | |
| 1554 | 12 | |
| 1540 | 14 | |
| 268 | 11 | G268S, |
| 1622 | 14 | |
| 1561 | 11 | |
| 1623 | 10 | c.4867delC, R1623X, R1623Q, R1623L, |