KCNQ1 Variant I204F

Summary of observed carriers, functional annotations, and structural context for KCNQ1 I204F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

78%

8/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

2

Publications with functional data

I204F 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 (%)
-3.41 0.901 2 0.891 83

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
32893267 2020 1 None 1 None
22949429 2012 1 None 1 None
20421371 2010 None None None None
19841300 2009 1 None 1 None
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 I204F.
Neighbour residue Distance (Å) Observed variants
204 0 I204M, I204F,
205 5 V205M,
203 5 L203P,
201 5 I201del,
207 6 V207M, V207L, V207L, V207L, V207L, V207del
200 6
208 7 A208V,
206 7 V206L,
202 7 D202N, D202H,
236 8 L236Q, L236R,
233 8 L233P,
199 9 S199A,
209 9 S209P,
232 10
240 10 H240R, H240P,
198 10 I198V, I198T,
237 10
197 10 P197L,
171 10
210 11 M210I, M210I, M210I,
211 11
194 11 A194P, A194T,
239 11
229 11 G229D,
164 12
167 12
168 12 G168R, G168R, G168R, G168R,
212 12
230 12
235 13 I235N,
196 13
234 13 Q234H, Q234H,
225 14 S225L, S225del,
195 14 R195Q, R195W,
213 14
275 14 F275del,
243 15 R243H, R243C, R243P, R243S,
193 15 F193L, F193L, F193L,
170 15
174 15 R174H, R174C, R174L,
238 15 M238V, M238L, M238L,
160 15 E160del, E160K, E160V,
226 15 A226V,
175 15 L175I,