SCN5A Variant G1433R

Summary of observed carriers, functional annotations, and structural context for SCN5A G1433R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/11 effective observations

Estimated BrS1 penetrance

45%

4/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

G1433R has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 4 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 (%)
-0.62 0.824 -2.64 0.666 70 7

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
23799537 2013 2 0 0 1 ERS
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 11 0 4 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
23799537 2013 HEK 15 11.65 -2.78

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 G1433R.
Neighbour residue Distance (Å) Observed variants
1355 9
1403 12
1357 9 A1357V,
1386 13
741 15 p.M741_T742delinsI ,
1430 9 D1430N,
1352 13
1426 14
1445 13 Y1445H,
1361 8
1444 15 L1444I,
739 11
1395 11
1397 13 c.4190delA, c.4189delT,
1380 15 p.N1380del, N1380K, N1380K,
1429 11
1442 11 Y1442C, Y1442N,
1398 13 V1398M,
1353 13 V1353M,
1358 7 G1358W, G1358R, G1358R,
1396 14
1362 11 R1362S, R1362S, c.4083delG,
1433 0 G1433R, G1433W, G1433V, G1433R,
1438 7 P1438L,
1388 10
1387 10 L1387F, L1387F,
1437 8
1431 5 S1431C,
805 14 S805L,
1383 15 Q1383X,
1359 5 K1359N, K1359M, K1359N,
1434 4 c.4299G>A, c.4299_4300insG, c.4299delG, c.4299+28C>T, c.4299+1G>T, c.4299+1delG, c.4300-2A>T, c.4299+2T>A, c.4300-1G>A, Y1434X,
1356 9 c.4066_4068delTT,
1435 6
1360 9 F1360C,
1401 14
1354 13
1427 11 A1427S, A1427E,
1446 12
1432 5 R1432S, R1432G, R1432S,
1389 13
1439 10 Q1439H, Q1439H, Q1439R,
740 14 p.N740del,
1443 9 N1443S,
1428 10 A1428V, A1428S,
1363 13 C1363Y,
1436 5
1402 13