SCN5A Variant I230T

Summary of observed carriers, functional annotations, and structural context for SCN5A I230T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/23 effective observations

Estimated BrS1 penetrance

9%

2/23 effective observations

Total carriers

13

0 BrS1 · 0 LQT3 · 13 unaffected

I230T has not been reported 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 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 (%)
-4.55 0.993 0.35 0.921 21 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
28739862 2017 2 0 0 1 SSS
20564468 2010 17 0 0 4 Conduction system disorder, ventricular arryhthmia during fever
Literature, cohort, and gnomAD – 13 13 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)
28739862 2017 hiPSC 17 10.2 2.5
20564468 2010 HEK 41 15.4 4.9

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 I230T.
Neighbour residue Distance (Å) Observed variants
848 6 I848F,
223 13 V223L,
839 14 L839P,
842 11
240 7 V240M,
231 5 c.692_693delCA,
193 9 W193R, W193X,
926 15
237 10
228 7 K228R,
138 10 M138I,
925 14 I925F,
227 6 L227P,
137 14 I137V,
234 10 P234S,
142 11
197 13
933 15
229 5
851 12 F851L, p.F851CfsX19, c.2552_2553dupGT, c.2550_2551dupGT,
196 12
852 11
224 12 L224F,
845 6 c.2533delG,
232 7 V232I, V232F,
244 12
191 15
134 14 N134S,
849 9
226 8 A226V, A226G,
241 11
235 10 c.703+1G>A, c.704-1G>C, G235R,
840 11
843 11 T843A,
930 13 c.2787+17_2787+18insACACACACACACACACACACACA, c.2788-6C>T,
837 14
239 9 I239V , I239V,
230 0 I230M, I230V, I230T,
139 14 p.I137_C139dup,
242 12 A242D,
841 9 p.N841TfsX2, N841K,
236 6
847 10
846 11 L846R
192 13
238 11
233 5
838 13
194 14
141 11 I141N, I141V,
135 15 M135V,
853 14
225 11 R225Q, R225W,
844 8 L844RfsX3,
850 13 V850M, c.2549_2550insTG,
243 11
145 13