SCN5A Variant I167L

Summary of observed carriers, functional annotations, and structural context for SCN5A I167L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

18%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

I167L 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 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 0.774 18 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 I167L.
Neighbour residue Distance (Å) Observed variants
198 13
147 14
164 6 F164L, F164L, F164L,
170 6 F170I,
228 14 K228R
138 11 M138I, M138I, M138I,
171 7
143 11
137 7 I137V,
142 13
197 12
163 6 c.486delC,
169 6
222 13 R222X, R222Q, R222L,
127 13
174 11 V174I,
133 10
132 13 c.393-5C>A,
160 10 p.V160fs,
134 12 N134S,
205 13 c.612-2A>G, Y205X,
166 4 A166T,
144 11
172 9
139 11 p.I137_C139dup,
165 6
204 12 A204T, c.611+1G>A, c.611+3_611+4dupAA, A204V,
162 11 Y162H, Y162C,
208 13 E208K,
136 9 L136P,
168 5
202 14 I202T,
175 12 K175N, K175N,
141 10 I141V, I141N,
135 14 M135V,
167 0
128 13 c.381dupT,
161 11 E161K, E161Q,
201 10
225 11 R225W, R225Q,
159 13 Y159C, Y159X,
173 11
200 13
145 15
140 7