SCN5A Variant H184R

Summary of observed carriers, functional annotations, and structural context for SCN5A H184R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

1%

0/11 effective observations

Estimated BrS1 penetrance

13%

1/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

H184R is present in 1 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 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 (%)
-1.45 0.642 -1.79 0.539 16 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 – 1 1 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 H184R.
Neighbour residue Distance (Å) Observed variants
192 15
175 11 K175N, K175N,
197 15
113 7 V113I, V113A,
194 11
188 6
178 8 A178G,
190 10 R190G, R190W, R190Q, R190L
128 14 c.381dupT,
179 6 R179X, R179Q,
177 10 L177P,
189 10
121 11 R121W, R121Q,
198 12
124 14 A124D,
118 14
125 13 V125L, V125L,
181 8
176 8
172 13
174 13 V174I,
185 5 A185T, A185V,
115 11 S115G,
186 8
182 7 C182R, C182Y,
173 13
112 7 Y112C,
114 7
184 0 H184R,
191 11
116 12
187 5 T187S, T187S, T187I,
180 4 G180V,
183 5