SCN5A Variant I94V

Summary of observed carriers, functional annotations, and structural context for SCN5A I94V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/13 effective observations

Estimated BrS1 penetrance

17%

2/13 effective observations

Total carriers

3

0 BrS1 · 0 LQT3 · 3 unaffected

I94V is present in 3 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 (%)
-0.56 0.009 2.03 0.313 43 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
24613995 2014 1 0 0 1 irritable bowel syndrome
Literature, cohort, and gnomAD – 3 3 0 0 –
Variant features alone – 15 13 0 2 – –

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)
24613995 2014 HEK 109 -0.5 -1.3 53

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 I94V.
Neighbour residue Distance (Å) Observed variants
79 15 P79A, P79S, P79H,
80 14
81 14
82 13 D82E, D82E,
83 13 p.L83WfsX14,
84 12 D84N, D84G,
85 11 P85T, P85S,
86 11 F86L, F86L, F86L,
87 10 Y87C,
88 9 S88G,
89 8
90 8 p.Q90WfsX14,
91 7
92 5 c.274-24C>T, T92I,
93 4 F93S,
94 0 I94V, I94S,
95 4 V95I, V95L, V95L,
96 5
97 7
98 8
99 8
100 9
101 10 T101I,
102 11
103 11
104 12 R104G, R104W, R104Q,
105 13
106 13 S106T,
107 14
108 14
109 15 N109K, N109K