SCN5A Variant D1423H

Summary of observed carriers, functional annotations, and structural context for SCN5A D1423H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/11 effective observations

Estimated BrS1 penetrance

21%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

D1423H 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 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 (%)
-5.99 1 -2.89 0.918 24 2

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 D1423H.
Neighbour residue Distance (Å) Observed variants
890 15 I890T,
901 12 E901K, S901L,
1417 14
1430 11 D1430N,
1426 6
1715 11
1361 14
1444 15 L1444I,
1440 12 W1440X,
1397 14 c.4189delT, c.4190delA,
1380 14 p.N1380del, N1380K, N1380K,
1429 11
1711 15 c.5131delG,
1450 12
1398 9 V1398M,
1411 11
886 15 H886P, H886Q, H886Q,
1410 15
1716 15 p.L1716SfsX71,
1714 9 D1714G,
376 15 R376C, R376H,
1362 11 c.4083delG, R1362S, R1362S,
1438 14 P1438L,
1423 0 D1423H,
1378 14 V1378M,
1431 13 S1431C,
1422 5 M1422R,
1418 12
902 15
373 14
1712 12 G1712S, G1712C,
1359 15 K1359M, K1359N, K1359N,
1356 14 c.4066_4068delTT,
898 12
893 11 R893C, R893H,
1412 14 L1412F,
1408 15 G1408R, G1408R,
889 13
1420 5 G1420R, G1420D, G1420V, G1420P,
1360 10 F1360C,
1401 12
1425 7
1399 11
1713 15
1427 7 A1427S, A1427E,
1424 5 I1424V,
1364 15 I1364V,
878 7 R878C, R878H, R878L,
1400 9 V1400I,
1718 12 S1718R, S1718R, S1718R
1421 8
1717 14 L1717P,
1416 14 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
877 13
879 9 W879R, W879R,
1686 13
375 14
1415 11
1428 9 A1428S, A1428V,
1419 10 K1419E,
1414 10 Q1414H, Q1414H,
1402 13
1413 15