SCN5A Variant R1432S

Summary of observed carriers, functional annotations, and structural context for SCN5A R1432S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

16%

1/13 effective observations

Estimated BrS1 penetrance

53%

6/13 effective observations

Total carriers

3

2 BrS1 · 1 LQT3 · 0 unaffected

R1432S 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 (%)
-4.55 0.947 -0.9 0.879 73 4

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
28341781 2017 1 0 1 0
19716085 2009 1 1 0 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 3 0 1 2 –
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)
28341781 2017
19716085 2009
20129283 2010

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 R1432S.
Neighbour residue Distance (Å) Observed variants
1355 12
1357 13 A1357V,
1386 11
1430 8 D1430N,
1426 13
1445 11 Y1445H,
1361 11
1444 12 L1444I,
1440 12 W1440X,
1382 13 S1382I,
1395 13
1380 14 p.N1380del, N1380K, N1380K,
1429 10
1442 6 Y1442C, Y1442N,
1358 12 G1358R, G1358W, G1358R,
1362 12 R1362S, c.4083delG, R1362S,
1433 5 G1433W, G1433R, G1433R, G1433V,
1438 7 P1438L,
1388 10
1387 8 L1387F, L1387F,
1437 7
1384 13 C1384Y,
1431 6 S1431C,
1383 11 Q1383X,
1359 9 K1359M, K1359N, K1359N,
1434 9 c.4299+1G>T, c.4300-1G>A, c.4299G>A, c.4299_4300insG, c.4300-2A>T, c.4299+2T>A, c.4299+28C>T, c.4299+1delG, c.4299delG, Y1434X,
1356 12 c.4066_4068delTT,
1435 10
1360 12 F1360C,
1427 11 A1427S, A1427E,
1446 12
1432 0 R1432S, R1432S, R1432G,
1389 14
1439 6 Q1439H, Q1439H, Q1439R,
1443 7 N1443S,
1441 11 E1441Q,
1428 11 A1428S, A1428V,
1363 13 C1363Y,
1436 5