SCN5A Variant T187I

Summary of observed carriers, functional annotations, and structural context for SCN5A T187I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

41%

4/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

T187I has not been reported 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 3 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 (%)
-5.49 0.999 -4.2 0.965 40 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
16325048 2005 2 0 1 1 SSS
29574140 2018 1 0 1 0
30371189 2018 2 0 2 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 12 0 3 – –

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)
16325048 2005 HEK 0
20384651 2010 0
20539757 2010
29574140 2018
30371189 2018

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 T187I.
Neighbour residue Distance (Å) Observed variants
192 10
175 11 K175N, K175N,
197 13
113 12 V113I, V113A,
194 8
188 5
178 12 A178G,
196 13
190 5 R190G, R190W, R190Q, R190L,
179 9 R179X, R179Q,
177 14 L177P,
189 6
198 11
181 12
176 10
172 14
174 15 V174I,
193 13 W193R, W193R, W193X,
185 5 A185T, A185V,
199 14 S199T
186 4
195 11
182 9 C182R, C182Y,
112 12 Y112C,
114 13
184 5 H184R,
191 7
187 0 T187S, T187S, T187I,
180 9 G180V,
183 7