KCNQ1 Variant R174C

Summary of observed carriers, functional annotations, and structural context for KCNQ1 R174C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

74%

10/14 effective observations

Total carriers

4

3 LQT1 · 1 unaffected

Functional studies

3

Publications with functional data

R174C is present in 1 alleles 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 (%)
-7.38 1.0 4 0.98 79

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 2 None 2 None
30758498 2019 7 None 7 None
29037160 2017 2 None 1 None
19934648 2010 None None None None
19716085 2009 1 None 1 None
17192539 2006 4 None 4 None
Literature, cohort, and gnomAD – 4 1 3 –
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 R174C.
Neighbour residue Distance (Å) Observed variants
174 0 R174H, R174C, R174L,
114 4
170 5
173 5
115 6 E115A, E115G,
171 6
175 6 L175I,
177 7 S177F,
172 7 V172M, V172E,
111 7 Y111C,
243 8 R243H, R243C, R243P, R243S,
193 8 F193L, F193L, F193L,
110 8 V110I,
202 8 D202N, D202H,
199 8 S199A,
178 9 A178T, A178del,
168 9 G168R, G168R, G168R, G168R,
176 9
113 9
169 9 T169M, T169R,
198 10 I198V, I198T,
167 10
126 10 H126D,
240 10 H240R, H240P,
112 10
125 10
194 10 A194P, A194T,
244 11
166 11 F166V,
107 11 Q107H, Q107H,
196 11
190 11 R190W, R190Q, R190L,
117 11 P117L,
203 11 L203P,
108 11 G108S,
116 11
184 12 Y184S, Y184C, Y184D, Y184H
180 12
179 12 G179S,
241 12 V241F, V241I, V241G,
181 12 R181C,
122 12 C122Y,
129 12 V129I,
201 12 I201del,
200 12
206 13 V206L,
242 13 D242N, D242Y,
197 13 P197L,
205 14 V205M,
189 14 G189R, G189R, G189E,
165 14 V165M,
106 14
164 14
245 14 G245V,
109 14 R109C, R109L,
191 14
237 15
239 15
204 15 I204M, I204F,
183 15 K183R,
163 15