SCN5A Variant M148I

Summary of observed carriers, functional annotations, and structural context for SCN5A M148I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

11%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

M148I 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 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 (%)
NA NA NA 0.926 6 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

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT3 BrS1 Other Other Disease
Literature, cohort, and gnomAD – 0 0 0 0 –
Variant features alone – 15 14 0 1 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 M148I.
Neighbour residue Distance (Å) Observed variants
888 14
154 12 P154L,
848 13 I848F,
223 7 V223L,
856 10 V856L, V856L,
862 14
859 10
153 12
149 5
147 5
164 10 F164L, F164L, F164L,
138 15 M138I, M138I, M138I,
227 13 L227P,
887 12
143 9
142 10
156 11 W156R, W156R, W156X,
158 13 K158T,
229 13
163 14 c.486delC,
216 15 S216X, S216L,
851 8 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L,
221 13
852 10
854 10 c.2559delT,
222 7 R222X, R222Q, R222L,
224 11 L224F,
155 13
857 12 G857D,
150 8
157 12 T157I,
882 14
160 11 p.V160fs,
881 14
849 15
226 10 A226G, A226V,
860 14 p.L860fsx89
858 9 M858L, M858L,
144 5
217 15
855 6
139 14 p.I137_C139dup,
148 0
165 14
884 9
204 13 A204T, c.611+1G>A, c.611+3_611+4dupAA, A204V,
162 15 Y162H, Y162C,
885 13
146 7 V146M, V146A,
847 14
203 15
168 13
152 9 D152N,
141 10 I141V, I141N,
853 13
161 10 E161K, E161Q,
219 9 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
225 11 R225W, R225Q,
151 6
218 14
159 15 Y159C, Y159X,
883 12
207 14
850 13 V850M, c.2549_2550insTG,
200 13
145 5
140 12
220 11 T220I,