SCN5A Variant I137N

Summary of observed carriers, functional annotations, and structural context for SCN5A I137N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

20%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

I137N has not been reported 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 2 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 0.967 22 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 13 0 2 – –

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 I137N.
Neighbour residue Distance (Å) Observed variants
231 11 c.692_693delCA,
198 13
124 14 A124D,
131 10
193 15 W193R, W193R, W193X,
164 10 F164L, F164L, F164L,
130 11
170 10 F170I,
228 9 K228R,
138 5 M138I, M138I, M138I,
227 14 L227P,
171 6
143 10
137 0 I137V,
142 9
197 10
229 11
129 12
163 12 c.486delC,
196 14
169 11
222 15 R222X, R222Q, R222L,
127 12
232 11 V232I, V232F
174 11 V174I,
133 6
132 9 c.393-5C>A,
160 15 p.V160fs,
134 6 N134S,
226 12 A226G, A226V,
166 11 A166T,
144 11
172 11
230 14 I230V, I230T, I230M,
139 6 p.I137_C139dup,
165 12
136 5 L136P,
168 7
175 10 K175N, K175N,
194 13
141 6 I141V, I141N,
135 8 M135V,
167 7
128 10 c.381dupT,
201 12
225 8 R225W, R225Q,
173 13
200 14
140 5
145 13