SCN5A Variant L1444I

Summary of observed carriers, functional annotations, and structural context for SCN5A L1444I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

12%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

L1444I is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-1.01 0.886 1.55 0.522 12 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
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 14 0 1 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 L1444I.
Neighbour residue Distance (Å) Observed variants
880 11
888 11
1355 14
890 13 I890T,
1430 9 D1430N,
1426 10
1445 6 Y1445H,
1447 6
1444 0 L1444I,
153 15
1440 9 W1440X,
149 14
1449 12 Y1449S, Y1449C,
1452 15
1429 6
1442 9 Y1442N, Y1442C,
1450 11
887 11
1451 12 V1451L, V1451D
886 7 H886P, H886Q, H886Q,
1433 15 G1433R, G1433R, G1433W, G1433V,
1438 13 P1438L,
1423 15 D1423H,
876 14
1431 11 S1431C,
1422 13 M1422R,
882 13
892 13 F892I,
881 14
1359 14 K1359M, K1359N, K1359N,
1356 13 c.4066_4068delTT,
889 9
1425 9
1427 11 A1427S, A1427E,
1446 7
1424 14 I1424V,
1432 12 R1432G, R1432S, R1432S,
1448 9 I1448L, I1448T,
1439 12 Q1439R, Q1439H, Q1439H,
884 11
878 12 R878C, R878H, R878L,
1421 15
885 6
1443 6 N1443S,
1441 8 E1441Q,
152 13 D152N,
877 14
879 10 W879R, W879R,
883 9
1428 9 A1428S, A1428V,