SCN5A Variant p.K1493del

Summary of observed carriers, functional annotations, and structural context for SCN5A p.K1493del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

16%

1/13 effective observations

Estimated BrS1 penetrance

36%

4/13 effective observations

Total carriers

3

2 BrS1 · 0 LQT3 · 1 unaffected

p.K1493del has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for Brugada syndrome and a Mild_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 2 individuals for Brugada syndrome and 1 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 26 33

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
23840796 2013 11 0 0 10 CCD
19029124 2009 1 0 1 0
19808440 2009 1 0 1 0
20129283 2010 1 0 1 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD 3 1 0 2
Variant features alone 15 12 1 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)
23840796 2013 HEK 19 0 0
19029124 2009
19808440 2009
20129283 2010
20129283 2010

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 p.K1493del.
Neighbour residue Distance (Å) Observed variants
1785 6
1778 9
1773 14
1486 11 F1486L, p.F1486del, F1486L, F1486L,
1652 15 M1652T, M1652R,
1866 13
1824 15 P1824A,
1777 8 V1777M, V1777L, V1777L,
1485 15
1487 12 M1487L, M1487L, M1487K,
1492 6
1477 14 K1477N, K1477N,
1491 7 Q1491H, Q1491H,
1863 14
1501 14 p.L1501_K1505del, L1501V,
1874 15
1862 10
1779 10 T1779M,
1493 0 p.K1493del, K1493X, K1493R,
1858 13
1865 12
1478 13 K1478E,
1776 11
1787 11 S1787N,
1786 9 c.5356_5357delCT, L1786Q, L1786R,
1861 13 V1861I, V1861F
1495 9 Y1495S,
1774 14 N1774D, c.5321_5324dupACTT,
1496 7
1474 14
1481 13 G1481R, G1481R, G1481E, G1481V,
1781 6 E1781G, E1781D, E1781D,
1499 12
1488 8 T1488R,
1784 6 E1784K, E1784X,
1498 11 M1498V, M1498T, M1498R,
1780 7 E1780G,
1788 14 c.5361_5364delTGAG,
1500 11 p.K1500del,
1859 14
1869 15
1791 14
1482 12
1868 12
1783 8
1775 14 F1775V, p.F1775LfsX15,
1484 15
1497 8
1490 6
1790 14 D1790N, D1790G, p.D1790del,
1483 13 Q1483H, Q1483H,
1494 8
1489 6 E1489D, E1489D,
1782 9