SCN5A Variant R1632L

Summary of observed carriers, functional annotations, and structural context for SCN5A R1632L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

11%

0/11 effective observations

Estimated BrS1 penetrance

49%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

R1632L has not been reported in gnomAD. This residue resides in a Hotspot region for Brugada syndrome and a Mild_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 (%)
-6.48 1 -4.07 0.972 62 15

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
21656940 2011 1 0 1 0
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD 1 0 0 1
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)
21656940 2011
30059973 2018

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 R1632L.
Neighbour residue Distance (Å) Observed variants
1525 13 V1525M, V1525A,
1627 11
1586 12
1567 14 F1567L, F1567L, F1567L,
1624 14 V1624I,
1536 12
1538 7
1531 9
1635 6
1587 15 F1587V,
1634 8 L1634P,
1534 8
1542 11
1575 12 C1575S, C1575S,
260 15
1571 11 F1571C,
1570 14 p.1570_F1571insI, I1570V, p.I1570dup,
1529 14
1599 14
1630 6 I1630V, I1630R,
1532 11 V1532I, V1532F,
1626 12 R1626C, R1626H, R1626P, R1626L,
1644 15 R1644C, R1644H, R1644L
1625 12
262 15 S262G,
1596 13 F1596I, F1596C,
1628 8
1589 9
1632 0 R1632C, R1632H, R1632L,
1597 13 V1597M,
1530 12
1539 9 C1539Y, C1539F,
1573 15
1535 5
1537 11
1594 9 F1594S,
1638 14 R1638X, R1638Q,
259 12
1588 14 T1588I,
1633 6
1591 5 W1591X,
1593 11 I1593M,
1595 7
1637 12
1636 8
263 13 V263I,
1629 5 R1629G, R1629X, R1629Q,
1574 10 c.4719C>T, E1574K,
1533 12 T1533I,
1541 12
1592 8
1578 11 c.4732_4733dupAA,
1540 13
1528 15
1631 5 G1631D,
1590 9
1647 15
1598 12 V1598A,
1577 15