SCN5A Variant G1740R

Summary of observed carriers, functional annotations, and structural context for SCN5A G1740R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/12 effective observations

Estimated BrS1 penetrance

50%

5/12 effective observations

Total carriers

2

2 BrS1 · 0 LQT3 · 0 unaffected

G1740R 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 (%)
-7.4 1 -0.52 0.982 48 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
15057319 2004 1 0 1 0
11901046 2002 1 0 1 0
19251209 2009 1 0 1 0
20129283 2010 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)
11901046 2002
19251209 2009
20129283 2010
15057319 2004 HEK-tSA202 0

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 G1740R.
Neighbour residue Distance (Å) Observed variants
1741 4 D1741Y, D1741E, D1741N, D1741E,
1745 14
1675 14
1743 7 G1743R, G1743R, G1743E,
1681 6 c.5040_5042delTTAinsC, Y1681F,
1694 13
1737 10 G1737D,
1226 14
1747 14 V1747M,
1695 11 Q1695X,
1688 15
1684 13 W1684R, W1684R,
1676 14 M1676I, M1676I, M1676T, M1676I,
1744 11 S1744I,
1721 14
1742 5
1733 9
1693 14
1738 7 S1738F, S1738T,
1680 7 A1680P, A1680T,
1719 13
1731 7
1728 14 C1728W, C1728R, C1728Y,
1690 15 D1690N, c.5068_5070delGA,
1678 11 N1678S,
1227 12
1300 14
1735 11
1730 11 P1730H, P1730L, P1730A,
1683 8
1739 5 R1739Q, R1739W,
1734 9
1677 12
1682 7
1722 13 N1722D,
1729 13 D1729N,
1740 0 G1740R, G1740R,
1720 12 c.5157delC,
1732 5
1736 13
1679 11
1685 14