SCN5A Variant E1441Q

Summary of observed carriers, functional annotations, and structural context for SCN5A E1441Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/11 effective observations

Estimated BrS1 penetrance

43%

4/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

E1441Q 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 3 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 (%)
-2.86 0.977 -1.59 0.957 54 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

Observed carriers by publication or cohort.
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 12 0 3

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)
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.

Previously observed variants near E1441Q.
Neighbour residue Distance (Å) Observed variants
880 10
1430 9 D1430N,
1426 10
1445 12 Y1445H
1447 13
1444 8 L1444I,
153 15
1440 4 W1440X,
1382 12 S1382I,
1380 14 p.N1380del, N1380K, N1380K,
1429 9
1442 5 Y1442N, Y1442C,
887 15
886 9 H886P, H886Q, H886Q,
1362 14 c.4083delG, R1362S, R1362S,
1438 11 P1438L,
1387 14 L1387F, L1387F,
1437 13
876 10
1431 12 S1431C,
882 11
1383 11 Q1383X,
881 15
889 14
1425 14
865 15
1427 12 A1427S, A1427E,
1446 14
1432 11 R1432G, R1432S, R1432S,
1439 7 Q1439R, Q1439H, Q1439H,
884 15
874 15 G874D,
878 11 R878C, R878H, R878L,
885 11
1443 9 N1443S,
1441 0 E1441Q,
152 13 D152N,
877 11
879 12 W879R, W879R,
883 10
875 12
1428 13 A1428S, A1428V,