SCN5A Variant V922I

Summary of observed carriers, functional annotations, and structural context for SCN5A V922I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

7%

0/11 effective observations

Estimated BrS1 penetrance

7%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

V922I is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for Brugada syndrome and a Non_Hotspot region for LQT3.

Variant features alone are equivalent to phenotyping 0 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 (%)
-0.89 0.027 0.61 0.718 7 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 15 0 0 – –

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 V922I.
Neighbour residue Distance (Å) Observed variants
891 6 I891N, I891T,
848 13 I848F,
223 15 V223L,
856 11 V856L, V856L,
890 10 I890T,
901 15 E901K, S901L,
888 12
919 6
363 15
896 10 C896S, C896S,
895 7 L895F,
894 6 I894M,
247 14 V247L, V247L,
372 13
926 6
928 9 L928P,
925 6 I925F,
366 12
887 12
933 15
851 13 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
897 9 G897R, G897R, G897E,
924 6 V924I,
927 8 N927S, N927K, N927K,
852 11
854 10 c.2559delT,
224 15 L224F,
860 14 p.L860fsx89,
845 13 c.2533delG,
857 11 G857D,
902 11
892 10 F892I,
881 13
849 8
898 12
893 11 R893C, R893H,
921 5
922 0 V922I,
920 7
889 13
900 12
930 10 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
1459 15 c.4376_4379delTCTT
918 6
855 13
917 10 L917V, L917R,
916 11
929 10
906 13
408 15
847 12
846 10 L846R,
903 11 p.M903CfsX29,
367 15 R367C, R367H, R367L,
853 6
370 12 T370M,
923 5
915 11 C915R,
899 9
850 8 V850M, c.2549_2550insTG,
914 13
243 14
932 13
861 13 p.F861WfsX90, c.2582_2583delTT,
907 15
931 11