SCN5A Variant A1698T

Summary of observed carriers, functional annotations, and structural context for SCN5A A1698T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/14 effective observations

Estimated BrS1 penetrance

24%

3/14 effective observations

Total carriers

4

1 BrS1 · 0 LQT3 · 3 unaffected

A1698T is present in 3 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 2 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 (%)
-2.43 1 -1.6 0.872 25 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
20129283 2010 1 0 1 0
29325976 2018 1 0 1 0
Literature, cohort, and gnomAD 4 3 0 1
Variant features alone 15 13 0 2

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)
20129283 2010
29325976 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 A1698T.
Neighbour residue Distance (Å) Observed variants
333 13 c.998+5G>A, c.998+1G>A,
1702 6
387 6
385 14 A385T,
391 13
330 11 S330F,
388 10 I388S,
1698 0 A1698T,
1220 13 G1220E,
1673 11
1675 13
1666 15
332 12 A332T,
1707 14
1694 9
1704 10 L1704H,
1226 11
1706 12 Q1706H, Q1706H,
1695 9 Q1695X,
1716 15 p.L1716SfsX71,
1688 14
1669 11
1671 15
329 14
1221 14 A1221V,
1668 10 M1668T,
1676 9 M1676I, M1676I, M1676I, M1676T,
1692 9
386 11 G386E, G386R, G386R,
1219 15 S1219N,
1672 9 S1672Y,
1693 8
378 12
1699 4
331 8
1665 12
379 13
1680 14 A1680P, A1680T,
1703 8
1701 5 M1701I, M1701I, M1701I,
1228 10 Y1228F, Y1228H, Y1228C,
1690 13 D1690N, c.5068_5070delGA,
1223 9 c.3667delG,
1697 4
389 13 Y389X, Y389H,
1222 14 p.L1222LfsX7, L1222R,
1227 11
393 14
390 9
394 14
383 14
1708 15 T1708I,
382 11
1696 5
1705 10
1689 13 D1689N,
1700 5
1677 15
1224 10
1670 14
381 15 c.1140+1G>A, c.1141-3C>A,
1225 14 E1225K, G1225K,
1691 9
1679 14
1667 15 V1667I,