SCN5A Variant V1400I

Summary of observed carriers, functional annotations, and structural context for SCN5A V1400I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

10%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

V1400I 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 (%)
-0.71 0.943 1.33 0.528 14 0

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 V1400I.
Neighbour residue Distance (Å) Observed variants
1355 15
1403 9
1357 12 A1357V,
1724 13
1417 14
1430 14 D1430N,
1352 13
1426 12
1406 10 G1406R, G1406R, G1406E,
1453 15
1715 11
1361 12
739 14
1745 14
1397 9 c.4189delT, c.4190delA,
1449 15 Y1449S, Y1449C,
1429 14
1723 10 T1723N,
1450 13
1725 15 P1725L,
1398 5 V1398M,
1411 6
1353 14 V1353M,
1407 7
1410 8
1716 14 p.L1716SfsX71,
1714 8 D1714G,
1358 12 G1358R, G1358R, G1358W,
1396 12
1438 15 P1438L,
1404 11
1423 9 D1423H,
1362 12 c.4083delG, R1362S, R1362S,
1721 10
1349 13
1431 13 S1431C,
1422 12 M1422R,
1418 15
1712 14 G1712S, G1712C,
1359 12 K1359M, K1359N, K1359N,
1356 11 c.4066_4068delTT,
1412 10 L1412F,
1719 13
1408 8 G1408R, G1408R,
1420 8 G1420R, G1420D, G1420V, G1420P,
1360 7 F1360C,
1401 5
1425 12
1399 6
1713 13
1427 9 A1427S, A1427E,
1424 6 I1424V,
1748 14 p.G1748del, G1748D,
738 15
1405 13 V1405M, V1405L, V1405L,
1409 12 Y1409C, Y1409X,
1400 0 V1400I,
1718 9 S1718R, S1718R, S1718R,
1421 12
1717 10 L1717P,
1416 13 c.4245+1G>A, c.4245+1G>C, c.4245+2T>A, A1416E, A1416G,
1752 15
1722 13 N1722D,
1686 13
1749 13 I1749N
1720 14 c.5157delC,
1415 11
1428 11 A1428S, A1428V,
1685 14
1419 13 K1419E,
1414 8 Q1414H, Q1414H,
1402 7
1413 11