SCN5A Variant K175N

Summary of observed carriers, functional annotations, and structural context for SCN5A K175N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

48%

5/11 effective observations

Total carriers

1

1 BrS1 · 0 LQT3 · 0 unaffected

K175N 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 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 (%)
-4.8 0.993 -4.94 0.798 76 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
20129283 2010 1 0 1 0
Literature, cohort, and gnomAD – 1 0 0 1 –
Variant features alone – 15 11 0 4 – –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Peak and late/persistent current values are relative to wild-type (100% indicates no change). V1/2 activation and inactivation denote the membrane potentials (mV) at which half-maximal current is achieved.

Published electrophysiology measurements.
PubMed ID Year Cell Type Peak Current (% WT) V1/2 Activation (mV) V1/2 Inactivation (mV) Late/Persistent Current (% WT)
32533946 2020 HEK 118 7.3 -9.1
20129283 2010

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 K175N.
Neighbour residue Distance (Å) Observed variants
121 11 R121Q, R121W,
198 7
124 9 A124D,
131 14
193 13 W193R, W193R, W193X,
195 13
130 13
114 13
170 9 F170I,
184 11 H184R,
228 12 K228R,
138 13 M138I, M138I, M138I,
183 15
171 5
137 10 I137V
197 8
129 10
196 12
169 10
177 8 L177P,
189 12
123 13 A123G, A123V,
127 10
125 9 V125L, V125L,
174 5 V174I,
133 9
182 14 C182R, C182Y,
132 15 c.393-5C>A,
191 11
134 10 N134S,
166 14 A166T,
179 7 R179Q, R179X,
172 5
185 10 A185V, A185T,
199 13 S199T,
165 14
180 9 G180V,
120 15
192 14
126 13 K126E,
136 14 L136P,
168 11
175 0 K175N, K175N,
202 14 I202T,
194 8
141 14 I141N, I141V,
188 7
167 12
178 7 A178G,
128 6 c.381dupT,
201 11
225 12 R225Q, R225W,
181 13
176 6
186 15
173 7
200 13
140 15
187 11 T187S, T187I, T187S,