SCN5A Variant L136I

Summary of observed carriers, functional annotations, and structural context for SCN5A L136I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

2%

0/10 effective observations

Estimated BrS1 penetrance

37%

3/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

L136I has not been reported in gnomAD. This residue resides in a 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 (%)
NA NA NA 0.326 57 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 12 0 3 – –

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 L136I.
Neighbour residue Distance (Å) Observed variants
231 14 c.692_693delCA,
124 15 A124D,
131 9
164 12 F164L, F164L, F164L,
130 10
170 11 F170I,
228 13 K228R,
138 7 M138I, M138I, M138I,
171 10
143 11
137 5 I137V,
142 10
197 15
229 14
129 13
163 13 c.486delC,
169 14
127 11
232 13 V232I, V232F
174 13 V174I,
133 6
132 5 c.393-5C>A,
134 7 N134S,
166 13 A166T,
144 13
172 15
139 5 p.I137_C139dup,
165 15
136 0 L136P,
168 11
175 14 K175N, K175N,
141 10 I141V, I141N,
135 5 M135V,
167 9
128 11 c.381dupT,
225 13 R225W, R225Q,
145 15
140 7