SCN5A Variant I1424V

Summary of observed carriers, functional annotations, and structural context for SCN5A I1424V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

15%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I1424V 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 (%)
-0.95 0.988 3.67 0.863 22 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 I1424V.
Neighbour residue Distance (Å) Observed variants
1355 13
1403 13
1357 13 A1357V,
896 15 C896S, C896S,
1417 12
1430 10 D1430N,
1352 12
1426 8
1406 14 G1406R, G1406R, G1406E,
1453 12
1715 13
1361 13
1447 13
1444 14 L1444I,
1440 14 W1440X,
1397 13 c.4189delT, c.4190delA,
1449 11 Y1449S, Y1449C,
1429 9
1450 8
1398 8 V1398M,
1411 7
1451 14 V1451L, V1451D,
1353 15 V1353M,
1407 11
1410 11
1714 9 D1714G,
1358 14 G1358R, G1358R, G1358W,
1362 12 c.4083delG, R1362S, R1362S,
1438 13 P1438L,
1348 14 F1348L, F1348L, F1348L,
1404 14
1423 5 D1423H,
1349 14
1431 11 S1431C,
1422 7 M1422R,
1418 11
892 14 F892I,
1712 14 G1712S, G1712C,
1359 12 K1359M, K1359N, K1359N,
1356 9 c.4066_4068delTT,
898 13
893 13 R893C, R893H,
1412 9 L1412F,
1408 10 G1408R, G1408R,
889 13
1420 6 G1420R, G1420D, G1420V, G1420P,
1360 8 F1360C,
1401 9
1425 6
1399 11
1713 14
1454 13
1427 6 A1427S, A1427E,
1446 13
1424 0 I1424V,
1448 15 I1448L, I1448T,
1409 14 Y1409C, Y1409X,
878 11 R878C, R878H, R878L,
1400 6 V1400I,
1718 13 S1718R, S1718R, S1718R
1421 7
1443 15 N1443S,
1717 14 L1717P,
1416 11 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
879 12 W879R, W879R,
1415 7
1428 7 A1428S, A1428V,
1419 10 K1419E,
1414 8 Q1414H, Q1414H,
1402 8
1413 11