SCN5A Variant N1380K

Summary of observed carriers, functional annotations, and structural context for SCN5A N1380K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/12 effective observations

Estimated BrS1 penetrance

64%

7/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

N1380K has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 5 individuals for Brugada syndrome and 0 individuals for LQT3.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density BrS (%) Penetrance Density LQT3 (%)
-5.36 1 -1.65 0.859 87 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

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
20491895 2011 1 0 1 0
22840528 2012 1 0 1 0
24721456 2014 1 0 1 0
30059973 2018 2 2 0 0
Literature, cohort, and gnomAD – 2 0 0 2 –
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.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
30059973 2018
20491895 2011
22840528 2012
24721456 2014
32533946 2020 HEK 0

Nearby variants

Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.

Previously observed variants near N1380K.
Neighbour residue Distance (Å) Observed variants
1386 7
1394 11 Y1394X,
1430 10 D1430N,
1426 11
1361 10
1440 11 W1440X,
1382 6 S1382I,
1395 10
1397 14 c.4190delA, c.4189delT,
1390 14
1380 0 p.N1380del, N1380K, N1380K,
1429 15
1442 14 Y1442C, Y1442N,
1398 13 V1398M,
1396 10
1362 6 R1362S, R1362S, c.4083delG,
1433 15 G1433R, G1433W, G1433V, G1433R,
1438 8 P1438L,
1388 13
1423 14 D1423H,
1387 11 L1387F, L1387F,
1378 8 V1378M,
1437 7
1384 12 C1384Y,
1431 13 S1431C,
1383 9 Q1383X,
1391 14 G1391R, G1391R,
1366 12 Q1366R, Q1366H, Q1366H,
1381 5
1360 13 F1360C,
1393 13 L1393X,
1427 12 A1427S, A1427E,
1385 11
1365 7 N1365S,
1432 14 R1432S, R1432G, R1432S,
1389 13
1439 9 Q1439H, Q1439H, Q1439R,
1364 6 I1364V,
878 14 R878C, R878L, R878H,
1441 14 E1441Q,
1379 5
1428 15 A1428V, A1428S
1363 6 C1363Y,
1436 14
1367 11