SCN5A Variant I891T

Summary of observed carriers, functional annotations, and structural context for SCN5A I891T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

19%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I891T is present in 1 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 (%)
-3.44 0.993 -1.78 0.914 23 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
Literature, cohort, and gnomAD – 1 1 0 0 –
Variant features alone – 15 13 0 2 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 I891T.
Neighbour residue Distance (Å) Observed variants
891 0 I891N, I891T,
880 12
888 6
848 12 I848F,
223 14 V223L,
856 10 V856L, V856L,
890 5 I890T,
901 13 E901K, S901L,
919 7
862 14
896 9 C896S, C896S,
859 14
895 7 L895F,
894 5 I894M,
1455 15
1447 12
372 14
926 9
928 14 L928P,
925 11 I925F,
887 6
1451 12 V1451L, V1451D,
886 10 H886P, H886Q, H886Q,
851 10 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
897 10 G897R, G897R, G897E,
924 12 V924I,
927 11 N927S, N927K, N927K,
852 10
854 6 c.2559delT,
845 14 c.2533delG,
1422 13 M1422R,
857 9 G857D,
1418 14
902 9
882 15
892 6 F892I,
881 9
849 9
898 10
893 8 R893C, R893H,
921 11
922 6 V922I,
860 13 p.L860fsx89,
920 12
889 7
900 13
930 13 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1459 14 c.4376_4379delTCTT
858 11 M858L, M858L,
918 9
855 10
1425 14
917 14 L917V, L917R,
865 14
1454 14
916 14
929 15
1448 15 I1448L, I1448T,
884 10
906 12
1421 13
885 12
847 10
846 10 L846R,
903 12 p.M903CfsX29,
853 6
877 15
879 11 W879R, W879R,
923 9
883 12
905 14
915 12 C915R,
899 11
850 6 V850M, c.2549_2550insTG,
914 14
861 11 p.F861WfsX90, c.2582_2583delTT,
931 13