SCN5A Variant V1532I

Summary of observed carriers, functional annotations, and structural context for SCN5A V1532I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

2/88 effective observations

Estimated BrS1 penetrance

0%

0/88 effective observations

Total carriers

78

0 BrS1 · 2 LQT3 · 76 unaffected

V1532I is present in 76 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
0.36 0.739 3.15 0.611 2 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
24631775 2014 1 0 0 1 SD
26746457 2016 1 1 0 0
19716085 2009 1 1 0 0
Literature, cohort, and gnomAD – 78 76 2 0 –
Variant features alone – 15 15 0 0 – –

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)
24631775 2014
26746457 2016
19716085 2009

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 V1532I.
Neighbour residue Distance (Å) Observed variants
1525 12 V1525M, V1525A,
1524 12 I1524T,
1567 15 F1567L, F1567L, F1567L,
1536 7
1538 11
1531 5
1635 11
1634 14 L1634P,
1534 7
1571 13 F1571C,
1527 9 K1527R,
1570 13 p.1570_F1571insI, I1570V, p.I1570dup,
1639 14 G1639A
1529 5
1526 12 T1526P,
1630 13 I1630V, I1630R,
1532 0 V1532I, V1532F,
1632 11 R1632C, R1632H, R1632L,
1530 7
1539 10 C1539Y, C1539F,
1573 15
1535 6
1537 10
1638 13 R1638X, R1638Q,
1633 11
1595 15
1637 13
1636 8
1629 14 R1629G, R1629X, R1629Q,
1574 12 c.4719C>T, E1574K,
1533 4 T1533I,
1541 15
1578 13 c.4732_4733dupAA,
1540 12
1528 7
1631 14 G1631D,
1577 14