SCN5A Variant Y168D

Summary of observed carriers, functional annotations, and structural context for SCN5A Y168D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

19%

1/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

Y168D 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 0.976 19 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 Y168D.
Neighbour residue Distance (Å) Observed variants
223 13 V223L,
198 10
147 13
164 6 F164L, F164L, F164L,
195 15
170 9 F170I,
228 11 K228R
138 10 M138I, M138I, M138I,
227 14 L227P,
171 6
143 11
137 7 I137V,
142 12
197 8
229 14
163 9 c.486delC,
196 12
169 6
222 10 R222X, R222Q, R222L,
224 13 L224F,
174 12 V174I,
133 11
160 11 p.V160fs,
134 12 N134S,
226 12 A226G, A226V,
205 11 c.612-2A>G, Y205X,
206 14
166 6 A166T,
144 9
172 8
199 11 S199T,
139 11 p.I137_C139dup,
148 13
165 5
204 9 A204T, c.611+1G>A, c.611+3_611+4dupAA, A204V,
162 11 Y162H, Y162C,
203 12
208 12 E208K,
136 11 L136P,
168 0
175 11 K175N, K175N,
202 11 I202T,
194 13
141 8 I141V, I141N,
135 14 M135V,
167 5
128 14 c.381dupT,
161 10 E161K, E161Q,
201 6
219 15 p.R219HfsX11, R219C, c.656_657insATTCA, R219H,
225 7 R225W, R225Q,
218 15
159 15 Y159C, Y159X,
176 14
207 13
173 11
200 9
140 7
145 13