SCN5A Variant I176V

Summary of observed carriers, functional annotations, and structural context for SCN5A I176V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/10 effective observations

Estimated BrS1 penetrance

48%

4/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

I176V 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 4 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 0.761 72 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 11 0 4 – –

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 I176V.
Neighbour residue Distance (Å) Observed variants
170 11 F170I,
168 14
175 6 K175N, K175N,
202 13 I202T
197 11
113 10 V113I, V113A,
129 14
194 10
188 7
178 6 A178G,
190 15 R190G, R190W, R190Q, R190L,
128 10 c.381dupT,
201 13
179 7 R179X, R179Q,
169 11
177 5 L177P,
189 11
123 13 A123G, A123V,
121 9 R121W, R121Q,
198 8
127 13
124 10 A124D,
118 14
125 11 V125L, V125L,
181 7
176 0
172 6
174 6 V174I,
185 7 A185T, A185V,
199 14 S199T,
133 14
115 13 S115G,
186 12
195 14
122 15
182 9 C182R, C182Y,
173 6
112 13 Y112C,
114 8
184 8 H184R,
191 13
116 14
187 10 T187S, T187S, T187I,
180 5 G180V,
120 13
183 11
171 9