SCN5A Variant c.5040_5042delTTAinsC

Summary of observed carriers, functional annotations, and structural context for SCN5A c.5040_5042delTTAinsC. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/11 effective observations

Estimated BrS1 penetrance

41%

4/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

c.5040_5042delTTAinsC 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 (%)
NA NA NA None 39 1

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
17897138 2007 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
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)
17897138 2007 HEK 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 c.5040_5042delTTAinsC.
Neighbour residue Distance (Å) Observed variants
1741 6 D1741E, D1741N, D1741E, D1741Y,
1675 12
1743 11 G1743R, G1743R, G1743E,
1681 0 c.5040_5042delTTAinsC, Y1681F,
1694 10
1737 13 G1737D,
1226 10
1695 6 Q1695X,
1688 12
1684 11 W1684R, W1684R,
1676 10 M1676I, M1676I, M1676I, M1676T,
1692 15
1744 13 S1744I,
1742 10
1733 14
1693 9
1699 13
1738 10 S1738T, S1738F,
1680 5 A1680P, A1680T,
1231 13 E1231K,
1719 13
1731 13
1228 11 Y1228C, Y1228F, Y1228H,
1690 10 c.5068_5070delGA, D1690N,
1678 12 N1678S,
1230 12 E1230K,
1227 6
1735 15
1229 12
1683 9
1696 11
1689 14 D1689N,
1739 8 R1739W, R1739Q,
1700 14
1734 14
1677 11
1682 6
1740 6 G1740R, G1740R,
1225 13 E1225K, G1225K,
1691 14
1720 13 c.5157delC,
1732 11
1679 10
1685 14