SCN5A Variant I890T

Summary of observed carriers, functional annotations, and structural context for SCN5A I890T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

5%

0/14 effective observations

Estimated BrS1 penetrance

46%

6/14 effective observations

Total carriers

4

3 BrS1 · 0 LQT3 · 1 unaffected

I890T 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 (%)
-4.64 0.993 4.3 0.921 52 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
23308164 2013 4 0 3 0
26173111 2015 1 0 1 0
Literature, cohort, and gnomAD – 4 1 0 3 –
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)
23308164 2013 HEK 69 4.7 0.7
26173111 2015

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 I890T.
Neighbour residue Distance (Å) Observed variants
891 5 I891N, I891T,
880 8
888 7
856 12 V856L, V856L,
890 0 I890T,
901 10 E901K, S901L,
919 8
862 12
896 11 C896S, C896S,
859 14
895 10 L895F,
1426 14
894 7 I894M,
1447 11
1444 13 L1444I,
372 14
1440 15 W1440X,
926 14
1429 15
1450 15
904 14 W904X,
887 5
1451 13 V1451L, V1451D
864 15
886 7 H886P, H886Q, H886Q,
851 13 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
897 11 G897R, G897R, G897E,
909 14
1423 15 D1423H,
927 14 N927S, N927K, N927K,
852 13
854 8 c.2559delT,
876 13
1422 10 M1422R,
857 9 G857D,
1418 14
902 6
882 12
892 8 F892I,
881 7
849 14
898 10
893 6 R893C, R893H,
921 14
922 10 V922I,
860 13 p.L860fsx89,
920 14
889 5
900 12
858 10 M858L, M858L,
918 11
855 11
1425 12
865 11
1454 15
916 14
1448 15 I1448L, I1448T,
884 10
906 10
910 15 S910L,
878 11 R878C, R878H, R878L,
1421 12
885 10
847 14
846 14 L846R,
903 11 p.M903CfsX29,
853 10
877 10
879 7 W879R, W879R,
923 12
883 10
905 10
915 11 C915R,
899 11
850 10 V850M, c.2549_2550insTG,
908 15
914 15
861 10 p.F861WfsX90, c.2582_2583delTT,
907 14