KCNQ1 Variant E146K

Summary of observed carriers, functional annotations, and structural context for KCNQ1 E146K. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

8%

1/16 effective observations

Total carriers

6

0 LQT1 · 6 unaffected

Functional studies

1

Publications with functional data

E146K is present in 2 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 1 individuals with LQT1 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-2.79 0.25 -1 0.676 6

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
29672598 2018 1 None None None
24596401 2014 5 4 None None
Literature, cohort, and gnomAD – 6 6 0 –
Variant features alone – 15 9 1 –

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 E146K.
Neighbour residue Distance (Å) Observed variants
146 0 E146K, E146G, E146Q,
149 6
147 6 Q147R,
145 6
144 7 T144A,
143 7 S143F, S143P, S143Y,
148 8
150 8 A150T,
142 10
297 10 G297S, G297D, G297R,
298 10 S298I, S298N,
152 10
153 10 T153M,
151 11
141 11 V141M,
140 12 S140G, S140R, S140R, S140R,
285 12
227 13
281 13 Y281C
294 13 V294M,
231 13 R231C, R231H, R231S,
300 13 A300T, A300S,
301 14
299 14
154 14
139 14
156 14
286 15
155 15