KCNQ1 Variant L134P

Summary of observed carriers, functional annotations, and structural context for KCNQ1 L134P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

68%

7/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

L134P has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 6 individuals with LQT1 and 4 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-5.93 0.999 -3 0.91 68

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
19716085 2009 1 None 1 None
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 4 6 –

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 L134P.
Neighbour residue Distance (Å) Observed variants
134 0 L134P,
133 4 V133I,
135 5
130 5
137 5 L137F, L137P,
131 5
138 7
132 7 I132L,
136 7
238 7 M238V, M238L, M238L,
129 9 V129I,
128 9 A128del,
139 9
127 10 F127L, F127L, F127L,
234 10 Q234H, Q234H,
237 10
235 10 I235N,
241 10 V241F, V241I, V241G,
140 11 S140G, S140R, S140R, S140R,
274 11 I274V,
141 11 V141M,
267 12 Y267C
271 12
239 12
240 12 H240R, H240P,
159 12 M159del,
270 12 F270S,
163 12
142 13
236 13 L236Q, L236R,
126 13 H126D,
160 14 E160del, E160K, E160V,
299 14
156 14
167 14
303 14 L303P,
275 14 F275del,
233 14 L233P,
125 14
123 14
273 14 L273F, L273V, L273R,
242 14 D242N, D242Y,
124 14
231 15 R231C, R231H, R231S,
143 15 S143F, S143P, S143Y,
230 15