SCN5A Variant M138I
Summary of observed carriers, functional annotations, and structural context for SCN5A M138I. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT3 penetrance
4%
0/11 effective observations
Estimated BrS1 penetrance
16%
1/11 effective observations
Total carriers
1
0 BrS1 · 0 LQT3 · 1 unaffected
Variant features alone are equivalent to phenotyping 1 individuals for Brugada syndrome and 0 individuals for LQT3.
In silico predictors
PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density BrS (%) | Penetrance Density LQT3 (%) |
---|---|---|---|---|---|
-3.17 | 0.801 | 2.72 | 0.886 | 21 | 0 |
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 |
---|---|---|---|---|---|---|---|
18378609 | 2008 | 1 | 0 | 0 | 1 | AF | |
Literature, cohort, and gnomAD | – | 1 | 1 | 0 | 0 | – | |
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.
PubMed ID | Year | Cell Type | Peak Current (% WT) | V1/2 Activation (mV) | V1/2 Inactivation (mV) | Late/Persistent Current (% WT) |
---|---|---|---|---|---|---|
18378609 | 2008 |
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 |
---|---|---|
848 | 13 | I848F, |
223 | 14 | V223L, |
231 | 8 | c.692_693delCA, |
131 | 11 | |
193 | 13 | W193R, W193R, W193X, |
164 | 12 | F164L, F164L, F164L, |
130 | 13 | |
170 | 15 | F170I, |
228 | 7 | K228R, |
138 | 0 | M138I, M138I, M138I, |
227 | 11 | L227P, |
171 | 10 | |
143 | 9 | |
137 | 5 | I137V, |
234 | 14 | P234S, |
142 | 6 | |
197 | 11 | |
229 | 6 | |
129 | 14 | |
851 | 15 | c.2552_2553dupGT, F851L, F851L, p.F851CfsX19, F851L, c.2550_2551dupGT, |
196 | 13 | |
224 | 14 | L224F, |
845 | 15 | c.2533delG, |
232 | 7 | V232F, V232I, |
133 | 9 | |
132 | 11 | c.393-5C>A, |
134 | 7 | N134S, |
226 | 9 | A226V, A226G, |
144 | 10 | |
172 | 15 | |
230 | 10 | I230M, I230T, I230V, |
139 | 5 | p.I137_C139dup, |
148 | 15 | |
165 | 15 | |
236 | 14 | |
146 | 13 | V146A, V146M, |
136 | 7 | L136P, |
168 | 10 | |
175 | 13 | K175N, K175N, |
233 | 11 | |
194 | 14 | |
141 | 5 | I141N, I141V, |
135 | 7 | M135V, |
167 | 11 | |
128 | 13 | c.381dupT, |
201 | 14 | |
225 | 8 | R225W, R225Q, |
844 | 14 | L844RfsX3, |
200 | 14 | |
145 | 10 | |
140 | 7 |