SCN5A Variant Q1414H

Summary of observed carriers, functional annotations, and structural context for SCN5A Q1414H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

16%

0/11 effective observations

Estimated BrS1 penetrance

25%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

Q1414H is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 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 (%)
-4.87 1 -3.53 0.902 35 26

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 13 0 2 – –

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 Q1414H.
Neighbour residue Distance (Å) Observed variants
896 13 C896S, C896S,
1417 6
1406 12 G1406R, G1406R, G1406E,
1457 13
1453 11
1757 14
1715 10
1449 14 Y1449S, Y1449C,
1756 10 I1756V,
1711 11 c.5131delG,
1450 12
1754 15
1707 12
1398 13 V1398M,
1411 5
1407 10
1458 12 S1458Y,
1410 7
1706 15 Q1706H, Q1706H,
1716 11 p.L1716SfsX71,
1714 6 D1714G,
897 14 G897R, G897R, G897E,
1348 14 F1348L, F1348L, F1348L,
1404 15
1423 10 D1423H,
1721 13
1349 14
1753 11 T1753A,
1422 10 M1422R,
1418 8
373 14
1712 9 G1712S, G1712C,
1341 15
1356 15 c.4066_4068delTT,
898 13
893 14 R893C, R893H,
1462 12
1412 7 L1412F,
1719 14
1408 9 G1408R, G1408R,
1709 14 p.T1709del, T1709R, T1709M,
1420 6 G1420R, G1420D, G1420V, G1420P,
1360 14 F1360C,
1755 14
1401 11
1425 12
1399 12
1713 7
1454 12
1427 14 A1427S, A1427E,
1424 8 I1424V,
1748 13 p.G1748del, G1748D,
1405 14 V1405M, V1405L, V1405L,
1409 9 Y1409C, Y1409X,
1400 8 V1400I,
1421 8
1718 11 S1718R, S1718R, S1718R,
1345 11 W1345C, W1345C,
1717 9 L1717P,
1751 15
1416 7 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1760 12
1752 11
1686 14
1761 13 c.5280delG, L1761F, L1761H
1749 12 I1749N,
375 14
1710 9 S1710L,
1720 14 c.5157delC,
1415 5
1428 14 A1428S, A1428V,
1419 6 K1419E,
1414 0 Q1414H, Q1414H,
1402 11
1413 5