KCNQ1 Variant R231S

Summary of observed carriers, functional annotations, and structural context for KCNQ1 R231S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

56%

6/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

R231S has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 5 individuals with LQT1 and 5 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-5.77 0.999 -2 0.965 58

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. BLAST-PSSM reflects evolutionary conservation; more negative values indicate rarer substitutions. Penetrance density summarises neighbouring residue risk (Kroncke et al. 2019).

Reported carrier data

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT1 Other Disease
19618328 2009 1 None 1 AF
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 5 5 –

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 R231S.
Neighbour residue Distance (Å) Observed variants
231 0 R231C, R231H, R231S,
230 6
229 6 G229D,
140 6 S140G, S140R, S140R, S140R,
228 6
227 6
234 7 Q234H, Q234H,
144 7 T144A,
299 7
226 7 A226V,
278 8 Y278H,
143 8 S143F, S143P, S143Y,
232 8
281 8 Y281C
141 8 V141M,
233 8 L233P,
235 9 I235N,
225 9 S225L, S225del,
282 9 L282P,
137 9 L137F, L137P,
285 10
136 10
156 11
298 11 S298I, S298N,
142 11
279 11 F279I,
222 11
277 11 S277L, S277del, S277P, S277W,
160 11 E160del, E160K, E160V,
145 11
275 11 F275del,
236 11 L236Q, L236R,
237 11
212 11
224 11 T224M,
139 11
274 12 I274V,
223 12
300 12 A300T, A300S,
153 12 T153M,
138 12
303 12 L303P,
297 12 G297S, G297D, G297R,
302 12 A302V, A302E, A302T,
152 12
280 12 V280A, V280E,
209 12 S209P,
149 12
283 13 A283G, A283T,
213 13
146 13 E146K, E146G, E146Q,
208 13 A208V,
276 13 S276del,
205 13 V205M,
238 14 M238V, M238L, M238L,
133 14 V133I,
286 14
221 14
301 14
296 14 F296S, F296L, F296L, F296L,
159 14 M159del,
157 14 F157C,
135 14
284 14 E284K,
148 14
155 14
154 14
217 15
134 15 L134P,
216 15 G216R,