SCN5A Variant R1629G

Summary of observed carriers, functional annotations, and structural context for SCN5A R1629G. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/12 effective observations

Estimated BrS1 penetrance

48%

5/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

R1629G 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 3 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 -4.41 0.96 51 10

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
19843921 2009 1 0 1 0
27232914 2016 1 0 1 0
Literature, cohort, and gnomAD 2 0 0 2
Variant features alone 15 12 0 3

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)
19843921 2009
27232914 2016

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 R1629G.
Neighbour residue Distance (Å) Observed variants
266 13 L266H,
1569 13 A1569P,
1544 14 T1544P,
1627 7
1586 12
1567 11 F1567L, F1567L, F1567L,
1624 10 V1624I,
1536 13
1538 5
1531 12
1566 15
1635 11
1568 11
1587 15 F1587V,
1634 13 L1634P
1543 14 V1543L, V1543L, V1543A,
1602 12
1534 9
1542 9
1601 12 L1601H,
1575 11 C1575S, C1575S,
1600 13
1571 8 F1571C,
1572 12
1564 13
1570 12 p.1570_F1571insI, I1570V, p.I1570dup,
1599 9
1545 12
1630 6 I1630V, I1630R,
1532 14 V1532I, V1532F,
1626 7 R1626C, R1626H, R1626P, R1626L,
267 14
1625 7
262 15 S262G,
1596 11 F1596I, F1596C,
1628 6
1589 12
1632 5 R1632C, R1632H, R1632L,
1539 9 C1539Y, C1539F,
1597 9 V1597M,
1530 13
1573 13
1535 8
1537 9
1594 7 F1594S,
259 13
1633 10
1591 7 W1591X,
1593 10 I1593M,
1595 5
1636 13
263 12 V263I,
1629 0 R1629G, R1629X, R1629Q,
1574 9 c.4719C>T, E1574K,
1533 13 T1533I,
1541 8
1592 9
1578 11 c.4732_4733dupAA,
1540 12
1631 8 G1631D,
1590 10
1622 11
1621 14
1598 7 V1598A,
1623 13 c.4867delC, R1623X, R1623Q, R1623L,