KCNQ1 Variant D202H

Summary of observed carriers, functional annotations, and structural context for KCNQ1 D202H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

61%

6/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

D202H has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 5 individuals with LQT1 and 5 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-6.42 1.0 -4 0.988 67

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
25444851 2015 None None None None
20421371 2010 None None None None
15176425 2004 1 None 1 None
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 5 5 –

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 D202H.
Neighbour residue Distance (Å) Observed variants
202 0 D202N, D202H,
201 5 I201del,
199 5 S199A,
240 5 H240R, H240P,
203 5 L203P,
198 6 I198V, I198T,
171 6
205 6 V205M,
200 7
204 7 I204M, I204F,
206 7 V206L,
167 8
174 8 R174H, R174C, R174L,
243 8 R243H, R243C, R243P, R243S,
168 9 G168R, G168R, G168R, G168R,
170 9
237 9
197 9 P197L,
236 9 L236Q, L236R,
239 9
194 9 A194P, A194T,
196 9
207 10 V207M, V207L, V207L, V207L, V207L, V207del,
193 11 F193L, F193L, F193L,
233 11 L233P,
175 11 L175I,
164 11
241 11 V241F, V241I, V241G,
172 11 V172M, V172E,
208 11 A208V,
115 11 E115A, E115G,
209 11 S209P,
242 11 D242N, D242Y,
169 12 T169M, T169R,
166 12 F166V,
114 12
244 12
173 12
238 12 M238V, M238L, M238L,
163 13
129 13 V129I,
133 13 V133I,
248 13 W248C, W248C, W248R, W248R
165 13 V165M,
235 13 I235N,
245 13 G245V,
126 13 H126D,
234 13 Q234H, Q234H,
232 13
210 13 M210I, M210I, M210I,
195 14 R195Q, R195W,
130 14
177 14 S177F,
111 14 Y111C,
125 15
191 15
160 15 E160del, E160K, E160V,
178 15 A178T, A178del,
190 15 R190W, R190Q, R190L,
176 15
230 15