KCNQ1 Variant V133I

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V133I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

40%

4/12 effective observations

Total carriers

2

1 LQT1 · 1 unaffected

Functional studies

1

Publications with functional data

V133I is present in 1 alleles in gnomAD. This residue resides in a 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 (%)
-0.89 0.991 5 0.778 44

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
27810088 2016 20 20 None None
19716085 2009 1 None 1 None
12877697 2003 1 1 None None
Literature, cohort, and gnomAD – 2 1 1 –
Variant features alone – 15 7 3 –

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 V133I.
Neighbour residue Distance (Å) Observed variants
133 0 V133I,
134 4 L134P,
132 5 I132L,
130 5
136 5
137 6 L137F, L137P,
135 6
237 6
238 6 M238V, M238L, M238L,
129 6 V129I,
131 7
234 7 Q234H, Q234H,
128 8 A128del,
163 9
240 9 H240R, H240P,
138 9
241 9 V241F, V241I, V241G,
235 9 I235N,
167 9
159 10 M159del,
139 10
239 10
236 10 L236Q, L236R,
160 10 E160del, E160K, E160V,
127 10 F127L, F127L, F127L,
140 10 S140G, S140R, S140R, S140R,
233 11 L233P,
126 11 H126D,
166 11 F166V,
156 12
205 12 V205M,
164 12
125 12
274 12 I274V,
271 12
230 12
267 13 Y267C
141 13 V141M,
162 13 V162M,
202 13 D202N, D202H,
232 13
242 13 D242N, D242Y,
170 13
243 13 R243H, R243C, R243P, R243S,
231 14 R231C, R231H, R231S,
275 14 F275del,
209 14 S209P,
206 14 V206L,
142 14
124 14
201 14 I201del,
123 14
155 15
161 15
165 15 V165M,
299 15
229 15 G229D,
270 15 F270S,
168 15 G168R, G168R, G168R, G168R,
158 15
143 15 S143F, S143P, S143Y,