SCN5A Variant T165I

Summary of observed carriers, functional annotations, and structural context for SCN5A T165I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

22%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

T165I 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 0.946 25 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 T165I.
Neighbour residue Distance (Å) Observed variants
223 14 V223L,
198 12
147 12
164 6 F164L, F164L, F164L,
209 12 N209S, N209T,
170 10 F170I,
138 15 M138I, M138I, M138I,
171 10
143 13
137 12 I137V,
158 11 K158T,
197 12
163 6 c.486delC,
169 6
222 9 R222X, R222Q, R222L,
174 14 V174I,
157 13 T157I,
160 9 p.V160fs,
205 8 c.612-2A>G, Y205X,
206 11
166 4 A166T,
144 10
172 10
199 13 S199T,
139 15 p.I137_C139dup,
148 14
165 0
210 14 I210T,
204 7 A204T, c.611+1G>A, c.611+3_611+4dupAA, A204V,
162 6 Y162H, Y162C,
203 12
208 7 E208K,
136 15 L136P,
168 5
202 10 I202T,
175 14 K175N, K175N,
141 12 I141V, I141N,
167 6
161 7 E161K, E161Q,
201 7
219 13 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
225 11 R225W, R225Q
218 13
159 11 Y159C, Y159X,
207 10
173 13
200 10
145 15
140 10