SCN5A Variant R179Q

Summary of observed carriers, functional annotations, and structural context for SCN5A R179Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/17 effective observations

Estimated BrS1 penetrance

17%

2/17 effective observations

Total carriers

7

0 BrS1 · 0 LQT3 · 7 unaffected

R179Q is present in 7 alleles 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 (%)
-3.81 0.999 -1.66 0.927 39 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
28704380 2017 1 0 0 1 SUNDS
Literature, cohort, and gnomAD – 7 7 0 0 –
Variant features alone – 15 13 0 2 – –

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)
28704380 2017

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 R179Q.
Neighbour residue Distance (Å) Observed variants
126 12 K126E,
175 7 K175N, K175N,
197 14
113 10 V113I, V113A,
129 10
194 11
188 8
178 3 A178G,
190 14 R190G, R190W, R190Q, R190L
128 8 c.381dupT,
117 14
179 0 R179X, R179Q,
119 14 P119S, P119L,
177 8 L177P,
189 13
123 12 A123G, A123V,
121 7 R121W, R121Q,
198 13
127 12
124 9 A124D,
118 13
125 7 V125L, V125L,
181 11
176 7
172 11
174 9 V174I,
185 10 A185T, A185V,
133 14
115 11 S115G,
186 13
130 15
182 12 C182R, C182Y,
173 11
112 9 Y112C,
114 8
184 6 H184R,
191 12
116 10
187 9 T187S, T187S, T187I,
180 6 G180V,
134 14 N134S,
170 15 F170I,
120 13
183 11
122 11
171 13