SCN5A Variant V918I

Summary of observed carriers, functional annotations, and structural context for SCN5A V918I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

34%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

V918I 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 0.667 48 2

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 – 0 0 0 0 –
Variant features alone – 15 12 0 3 – –

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 V918I.
Neighbour residue Distance (Å) Observed variants
891 9 I891T, I891N,
888 15
223 14 V223L,
856 8 V856L, V856L,
890 11 I890T,
901 15 S901L, E901K,
919 4
862 13
363 13
859 13
895 13 L895F,
894 10 I894M,
926 12
928 14 L928P,
925 10 I925F,
904 13 W904X,
366 14
887 12
864 14
851 15 c.2550_2551dupGT, F851L, F851L, c.2552_2553dupGT, p.F851CfsX19, F851L,
897 14 G897R, G897E, G897R,
221 12
924 10 V924I,
909 14
927 14 N927K, N927K, N927S,
852 11
854 10 c.2559delT,
224 14 L224F,
857 8 G857D,
902 10
881 11
849 12
898 15
893 14 R893H, R893C,
921 5
922 6 V922I,
860 8 p.L860fsx89,
911 13 G911E,
920 6
900 13
858 13 M858L, M858L,
217 14
918 0
855 12
917 5 L917V, L917R,
865 14
913 9
916 7
912 12 Q912R,
906 9
910 12 S910L,
903 9 p.M903CfsX29,
853 7
923 10
905 14
915 6 C915R,
899 10
850 12 V850M, c.2549_2550insTG,
914 6
861 8 c.2582_2583delTT, p.F861WfsX90,
220 12 T220I,
907 10