SCN5A Variant V232I

Summary of observed carriers, functional annotations, and structural context for SCN5A V232I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/48 effective observations

Estimated BrS1 penetrance

7%

3/48 effective observations

Total carriers

38

2 BrS1 · 0 LQT3 · 36 unaffected

V232I is present in 36 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 1 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 (%)
-0.98 0.454 0.41 0.73 15 3

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
18599870 2008 1 0 1 0
20129283 2010 1 0 1 0
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 38 36 0 2 –
Variant features alone – 15 14 0 1 – –

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)
18599870 2008 tsA201 100 0
20129283 2010
20129283 2010

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 V232I.
Neighbour residue Distance (Å) Observed variants
848 11 I848F
842 14
240 12 V240M,
231 4 c.692_693delCA,
131 12
193 13 W193R, W193R, W193X,
237 11
228 8 K228R,
138 7 M138I, M138I, M138I,
227 11 L227P,
143 14
137 11 I137V,
234 7 P234S,
142 10
197 15
229 6
845 11 c.2533delG,
232 0 V232I, V232F,
133 14
132 14 c.393-5C>A,
134 10 N134S,
849 15
226 11 A226G, A226V,
235 9 c.703+1G>A, G235R, G235R, c.704-1G>C,
840 12
843 14 T843A,
837 13
239 13 I239V, I239V ,
230 7 I230V, I230T, I230M,
139 10 p.I137_C139dup,
841 10 p.N841TfsX2, N841K, N841K,
236 8
847 14
136 13 L136P,
238 14
233 5
838 14
141 11 I141V, I141N,
135 9 M135V,
225 13 R225W, R225Q,
844 9 L844RfsX3,
145 14
140 13