SCN5A Variant Y1445H

Summary of observed carriers, functional annotations, and structural context for SCN5A Y1445H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/19 effective observations

Estimated BrS1 penetrance

9%

1/19 effective observations

Total carriers

9

0 BrS1 · 0 LQT3 · 9 unaffected

Y1445H is present in 9 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 (%)
-4.72 0.961 -0.4 0.94 14 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 – 9 9 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 Y1445H.
Neighbour residue Distance (Å) Observed variants
888 13
1355 11
1430 12 D1430N,
1352 14
1426 14
1445 0 Y1445H,
1447 7
1444 6 L1444I,
1351 14 M1351V, M1351R,
1440 14 W1440X,
1449 11 Y1449S, Y1449C,
1452 13
1429 8
1442 10 Y1442N, Y1442C,
806 13 V806M,
1450 12
1451 12 V1451L, V1451D
886 12 H886P, H886Q, H886Q,
1433 13 G1433R, G1433R, G1433W, G1433V,
1431 11 S1431C,
805 13 S805L,
1359 14 K1359M, K1359N, K1359N,
1356 12 c.4066_4068delTT,
889 13
1425 12
1427 14 A1427S, A1427E,
1446 4
1432 11 R1432G, R1432S, R1432S,
1448 8 I1448L, I1448T,
1439 14 Q1439R, Q1439H, Q1439H,
884 13
885 9
1443 5 N1443S,
1441 12 E1441Q,
152 15 D152N,
883 13
1428 11 A1428S, A1428V,
804 14