SCN5A Variant D1690N

Summary of observed carriers, functional annotations, and structural context for SCN5A D1690N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/13 effective observations

Estimated BrS1 penetrance

52%

6/13 effective observations

Total carriers

3

2 BrS1 · 0 LQT3 · 1 unaffected

D1690N is present in 1 alleles 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 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 (%)
-4.79 1 -0.31 0.838 72 0

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
23085483 2013 1 0 1 0
26173111 2015 1 0 1 0
29325976 2018 1 0 1 0
Literature, cohort, and gnomAD 3 1 0 2
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)
26173111 2015
29325976 2018
23085483 2013 CHO 20 4.7 3.2
30232268 2018 CHO 52
27108952 2016 HEK 23 7 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 D1690N.
Neighbour residue Distance (Å) Observed variants
333 8 c.998+1G>A, c.998+5G>A,
1702 13
326 12
387 14
1741 12 D1741N, D1741Y, D1741E, D1741E,
1715 15
1687 10
330 14 S330F,
1698 13 A1698T,
334 9 c.999-424_1338+81del,
332 11 A332T,
1681 10 c.5040_5042delTTAinsC, Y1681F,
1694 11
327 14
1695 8 Q1695X,
384 15 S384T,
1716 13 p.L1716SfsX71,
1688 7
1684 5 W1684R, W1684R,
329 15
1676 15 M1676I, M1676I, M1676I, M1676T,
1692 8
386 15 G386E, G386R, G386R,
1693 6
1699 9
331 11
379 12
1680 12 A1680T, A1680P,
1703 12
1719 12
335 12 C335S, C335R, C335S,
325 14 L325R,
1228 13 Y1228C, Y1228F, Y1228H,
1690 0 c.5068_5070delGA, D1690N
324 12
1227 12
383 10
1683 10
382 13
1696 11
1689 5 D1689N,
1739 14 R1739Q, R1739W,
1700 13
1682 11
336 12 P336L,
1686 12
1740 15 G1740R, G1740R,
1691 6
1720 15 c.5157delC,
1679 14
1685 11