SCN5A Variant T220I

Summary of observed carriers, functional annotations, and structural context for SCN5A T220I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

0%

0/211 effective observations

Estimated BrS1 penetrance

2%

3/211 effective observations

Total carriers

201

2 BrS1 · 0 LQT3 · 199 unaffected

T220I is present in 197 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 (%)
-5.85 0.999 0.82 0.961 16 8

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
14523039 2003 2 0 0 1 SSS
15671429 2005 1 0 0 1 DCM, Afib, Heart block
21273195 2011 1 0 1 0
22677073 2012 1 0 0 1 SUDS
24144883 2014 1 0 0 1 AF
25163546 2015 1 0 0 1 DCM
25171853 2014 1 0 0 1 Atrial standstill
26884609 2016 3 0 0 2 DCM
23571586 2013 1 0 0 1 stillbirth, SUDS
26636822 2015 1 0 0 1 congenital complete heart block
22685113 2012 1 0 0 1 AF
20129283 2010 1 0 1 0
20129283 2010 1 0 1 0
29325976 2018 1 0 1 0
Literature, cohort, and gnomAD – 201 199 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)
24613995 2014 HEK 48 -2.1 -7.4 62
14523039 2003 HEK-tSA201 50 0.9 -4.4
20384651 2010 65 -1.8 -6.4
15671429 2005
15671436 2005
21273195 2011
22677073 2012
24144883 2014
25163546 2015
25171853 2014
26884609 2016
20539757 2010
23571586 2013
24059039 2013
26636822 2015
26771585 2016
22685113 2012 HEK
20129283 2010
20129283 2010
29325976 2018
32533946 2020 HEK 87 -2.7 -3.7

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 T220I.
Neighbour residue Distance (Å) Observed variants
223 7 V223L,
856 5 V856L, V856L,
919 15
862 11
859 5
149 15
863 12
227 14 L227P,
887 14
864 14
216 6 S216X, S216L,
851 13 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
221 4
196 14
852 10
854 11 c.2559delT,
222 7 R222X, R222Q, R222L,
224 9 L224F,
213 14
857 8 G857D,
881 13
226 13 A226G, A226V,
921 14
860 6 p.L860fsx89,
206 12
214 13
858 9 M858L, M858L,
144 14
217 4
918 12
855 8
917 14 L917V, L917R
913 14
199 13 S199T,
148 11
884 15
204 11 A204T, c.611+1G>A, c.611+3_611+4dupAA, A204V,
910 14 S910L,
203 9
208 15 E208K,
202 14 I202T,
853 11
161 14 E161K, E161Q,
201 14
219 6 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
225 13 R225W, R225Q,
151 13
218 7
207 11
915 14 C915R,
212 13 L212Q, L212P,
215 9 p.L215CfsX10,
914 11
200 10
861 9 p.F861WfsX90, c.2582_2583delTT,
145 14
220 0 T220I,