SCN5A Variant K228R

Summary of observed carriers, functional annotations, and structural context for SCN5A K228R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT3 penetrance

10%

0/11 effective observations

Estimated BrS1 penetrance

9%

0/11 effective observations

Total carriers

1

0 BrS1 · 0 LQT3 · 1 unaffected

K228R 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 0 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 (%)
-2.93 0.993 6.54 0.843 12 4

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 15 0 0 – –

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 K228R.
Neighbour residue Distance (Å) Observed variants
848 10 I848F,
223 11 V223L,
240 12 V240M,
231 6 c.692_693delCA,
198 12
131 15
193 7 W193R, W193R, W193X,
164 15 F164L, F164L, F164L,
195 12
237 13
228 0 K228R,
138 7 M138I, M138I, M138I,
227 6 L227P,
143 14
171 11
137 9 I137V,
234 14 P234S,
142 10
197 7
229 6
851 13 c.2550_2551dupGT, F851L, p.F851CfsX19, c.2552_2553dupGT, F851L, F851L
221 15
196 8
852 12
222 14 R222X, R222Q, R222L,
224 9 L224F,
845 12 c.2533delG,
232 8 V232I, V232F,
133 13
191 12
134 10 N134S,
849 13
226 6 A226G, A226V,
235 14 c.703+1G>A, G235R, G235R, c.704-1G>C,
144 12
172 14
230 7 I230V, I230T, I230M,
199 12 S199T,
139 12 p.I137_C139dup,
236 11
847 15
192 11
136 13 L136P,
168 11
175 12 K175N, K175N,
233 11
194 9
141 7 I141V, I141N,
188 14
135 12 M135V,
167 14
128 14 c.381dupT,
201 12
225 6 R225W, R225Q,
844 14 L844RfsX3,
200 11
145 12
140 11