SCN5A Variant R121Q

Summary of observed carriers, functional annotations, and structural context for SCN5A R121Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

3%

0/13 effective observations

Estimated BrS1 penetrance

48%

6/13 effective observations

Total carriers

3

2 BrS1 · 0 LQT3 · 1 unaffected

R121Q is present in 1 alleles in gnomAD. This residue resides in a 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 (%)
-3.79 1 1.75 0.963 65 1

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
24529773 2014 2 0 0 2 SUNDS
20129283 2010 1 0 1 0
20129283 2010 1 0 1 0
30059973 2018 1 1 0 0
Literature, cohort, and gnomAD – 3 1 0 2 –
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)
24529773 2014
20129283 2010
20129283 2010
30059973 2018

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 R121Q.
Neighbour residue Distance (Å) Observed variants
126 9 K126E,
175 11 K175N,
113 10 V113I, V113A,
129 12
188 14
178 5 A178G,
128 10 c.381dupT,
117 8
179 7 R179X, R179Q,
119 7 P119L, P119S,
177 6 L177P,
123 7 A123G, A123V,
121 0 R121Q, R121W,
127 11
124 6 A124D,
118 6
125 6 V125L,
181 11
176 9
172 14
174 9 V174I,
185 14 A185T, A185V,
115 6 S115G,
182 14 C182Y, C182R,
173 11
112 10 Y112C,
114 6
184 11 H184R,
170 14 F170I,
116 6
180 8 G180V,
120 6
183 14
122 5