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
Variant features alone are equivalent to phenotyping 3 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico 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
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.
Nearby variants
Neighbouring residues within 15 Ångström provide structural context. Variants listed in the right-most column have been observed clinically or in gnomAD.
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 | R190L, R190W, R190G, R190Q, |
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 |