SCN5A Variant V174D

Summary of observed carriers, functional annotations, and structural context for SCN5A V174D. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

4%

0/10 effective observations

Estimated BrS1 penetrance

23%

2/10 effective observations

Total carriers

0

0 BrS1 · 0 LQT3 · 0 unaffected

V174D 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 0.975 27 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 V174D.
Neighbour residue Distance (Å) Observed variants
121 9 R121W, R121Q,
198 11
124 6 A124D,
131 14
115 15 S115G,
114 12
130 12
170 6 F170I,
184 13 H184R,
122 13
171 6
137 11 I137V,
197 12
129 10
119 14 P119S, P119L,
169 9
177 5 L177P,
123 9 A123G, A123V,
127 7
125 8 V125L, V125L,
174 0 V174I,
133 8
132 14 c.393-5C>A,
116 15
134 11 N134S,
166 12 A166T,
179 9 R179X, R179Q,
172 6
185 13 A185T, A185V,
165 14
180 10 G180V,
120 11
126 11 K126E,
136 13 L136P,
168 12
175 5 K175N, K175N,
194 12
188 11
167 11
178 6 A178G,
128 6 c.381dupT,
201 13
118 14
181 13
176 6
173 5
187 15 T187S, T187S, T187I