KCNQ1 Variant L233P

Summary of observed carriers, functional annotations, and structural context for KCNQ1 L233P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

28%

3/11 effective observations

Total carriers

1

0 LQT1 · 1 unaffected

Functional studies

0

Publications with functional data

L233P is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 3 individuals with LQT1 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-6.36 1.0 -4 0.925 33

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
Literature, cohort, and gnomAD – 1 1 0 –
Variant features alone – 15 7 3 –

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 L233P.
Neighbour residue Distance (Å) Observed variants
233 0 L233P,
232 5
205 5 V205M,
230 5
236 5 L236Q, L236R,
229 5 G229D,
234 5 Q234H, Q234H,
237 5
209 6 S209P,
208 7 A208V,
235 7 I235N,
204 8 I204M, I204F,
231 8 R231C, R231H, R231S,
206 9 V206L,
212 9
160 9 E160del, E160K, E160V,
226 9 A226V,
225 9 S225L, S225del,
207 10 V207M, V207L, V207L, V207L, V207L, V207del,
201 10 I201del,
164 10
240 10 H240R, H240P,
136 10
278 10 Y278H,
239 10
228 10
137 10 L137F, L137P,
213 10
275 11 F275del,
202 11 D202N, D202H,
238 11 M238V, M238L, M238L,
211 11
133 11 V133I,
140 11 S140G, S140R, S140R, S140R,
167 11
210 11 M210I, M210I, M210I,
163 11
203 11 L203P,
227 11
156 12
161 13
274 13 I274V,
279 13 F279I,
159 13 M159del,
221 13
222 13
282 13 L282P,
224 14 T224M,
200 14
299 14
271 14
168 14 G168R, G168R, G168R, G168R,
134 14 L134P,
214 14 C214Y,
157 14 F157C,
198 14 I198V, I198T,
132 14 I132L,
141 14 V141M,
165 14 V165M,
162 14 V162M,
143 14 S143F, S143P, S143Y,
130 14
199 15 S199A,
139 15
216 15 G216R,
215 15 V215M, V215G, V215L, V215L,
135 15
241 15 V241F, V241I, V241G
223 15
166 15 F166V,
144 15 T144A,
171 15