SCN5A Variant I894M

Summary of observed carriers, functional annotations, and structural context for SCN5A I894M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

6%

0/11 effective observations

Estimated BrS1 penetrance

19%

2/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

I894M is present in 1 alleles 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 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 (%)
-2.25 0.998 1.13 0.777 28 5

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 I894M.
Neighbour residue Distance (Å) Observed variants
891 5 I891N, I891T,
880 14
888 10
856 14 V856L, V856L,
890 7 I890T,
901 10 E901K, S901L,
919 6
363 14
896 7 C896S, C896S,
895 5 L895F,
894 0 I894M,
372 9
926 9
371 14 Q371E,
928 11 L928P,
925 11 I925F,
904 13 W904X,
366 13
887 10
1451 14 V1451L, V1451D,
886 13 H886P, H886Q, H886Q,
1458 14 S1458Y,
851 14 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
897 5 G897R, G897R, G897E,
924 10 V924I,
927 8 N927S, N927K, N927K,
852 14
854 11 c.2559delT,
1422 12 M1422R,
857 12 G857D,
1418 11
902 7
892 7 F892I,
373 12
881 12
849 12
898 6
893 5 R893C, R893H,
921 10
922 6 V922I,
920 9
889 10
900 9
930 13 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1459 13 c.4376_4379delTCTT
918 10
855 15
1425 14
917 13 L917V, L917R,
1454 13
916 12
929 13
884 15
906 12
878 15 R878C, R878H, R878L,
1421 11
847 14
846 12 L846R,
903 9 p.M903CfsX29,
367 12 R367C, R367H, R367L,
853 9
370 11 T370M,
879 11 W879R, W879R,
923 6
905 13
915 12 C915R,
899 6
850 9 V850M, c.2549_2550insTG,
914 15
932 15
861 14 p.F861WfsX90, c.2582_2583delTT,
1419 14 K1419E,
907 14
931 11