KCNQ1 Variant L236R

Summary of observed carriers, functional annotations, and structural context for KCNQ1 L236R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

75%

8/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

2

Publications with functional data

L236R has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

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

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-5.83 1.0 1 0.963 78

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 0 1 –
Variant features alone – 15 3 7 –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Functional assay results from published electrophysiology studies. HM indicates homomeric channels, HT indicates heteromeric channels.

Homomeric channel data

Published electrophysiology measurements (homomeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

Heteromeric channel data

Published electrophysiology measurements (heteromeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

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 L236R.
Neighbour residue Distance (Å) Observed variants
236 0 L236Q, L236R,
235 5 I235N,
233 5 L233P,
232 5
239 5
237 6
205 6 V205M,
201 7 I201del,
240 7 H240R, H240P,
234 7 Q234H, Q234H,
238 7 M238V, M238L, M238L,
275 7 F275del,
204 8 I204M, I204F,
202 9 D202N, D202H,
229 9 G229D,
271 9
278 10 Y278H,
230 10
274 10 I274V,
133 10 V133I,
208 10 A208V,
137 10 L137F, L137P,
198 10 I198V, I198T,
209 11 S209P,
206 11 V206L,
241 11 V241F, V241I, V241G,
231 11 R231C, R231H, R231S,
200 11
203 12 L203P,
272 12 G272D, G272S, G272V,
167 12
279 12 F279I,
136 12
248 12 W248C, W248C, W248R, W248R,
242 12 D242N, D242Y,
199 12 S199A,
130 12
207 12 V207M, V207L, V207L, V207L, V207L, V207del,
197 12 P197L,
267 13 Y267C
160 13 E160del, E160K, E160V,
134 13 L134P,
164 13
243 13 R243H, R243C, R243P, R243S,
140 13 S140G, S140R, S140R, S140R,
276 13 S276del,
268 13 I268V, I268S,
277 14 S277L, S277del, S277P, S277W,
163 14
228 14
225 14 S225L, S225del,
212 14
226 14 A226V,
273 14 L273F, L273V, L273R,
299 14
129 14 V129I,
282 14 L282P,
132 14 I132L,
269 15 G269D, G269S, G269del,
171 15
332 15
245 15 G245V,