SCN5A Variant R1739Q

Summary of observed carriers, functional annotations, and structural context for SCN5A R1739Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/15 effective observations

Estimated BrS1 penetrance

9%

1/15 effective observations

Total carriers

5

0 BrS1 · 0 LQT3 · 5 unaffected

R1739Q is present in 4 alleles in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 1 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 (%)
-1.81 0.978 0.16 0.579 14 5

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
15996170 2005 1 0 0 1 DCM, CHF
26746457 2016 1 0 0 0
Literature, cohort, and gnomAD – 5 5 0 0 –
Variant features alone – 15 14 0 1 – –

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)
15996170 2005
26746457 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 R1739Q.
Neighbour residue Distance (Å) Observed variants
1727 15
1739 0 R1739W, R1739Q,
1734 12
1737 8 G1737D,
1695 13 Q1695X,
1684 12 W1684R, W1684R,
1682 9
1741 4 D1741N, D1741Y, D1741E, D1741E,
1731 8
1728 15 C1728R, C1728Y, C1728W,
1690 14 c.5068_5070delGA, D1690N,
1744 14 S1744I
1729 12 D1729N,
1227 14
1740 5 G1740R, G1740R,
1742 8
1735 11
1733 10
1732 8
1736 12
1743 11 G1743R, G1743R, G1743E,
1730 10 P1730A, P1730H, P1730L,
1679 15
1685 14
1683 8
1738 6 S1738T, S1738F,
1680 11 A1680T, A1680P,
1681 8 c.5040_5042delTTAinsC, Y1681F,