KCNQ1 Variant Y111C

Summary of observed carriers, functional annotations, and structural context for KCNQ1 Y111C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

91%

96/106 effective observations

Total carriers

96

90 LQT1 · 6 unaffected

Functional studies

1

Publications with functional data

Y111C is present in 2 alleles 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 (%)
-6.82 1.0 -4 0.95 81

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
33382510 2021 1 1 None None
32893267 2020 9 None 9 None
32173736 2020 4 3 1 None
30758498 2019 1 None 1 None
29270100 2017 None None None None
28720088 2017 148 None 74 None
27041096 2016 1 None None None
26019114 2015 70 None None None
25471708 2015 None None None JLNS w/ vestibular DFx
24667783 2015 1 None 1 None
24052033 2013 60 None None None
22677073 2012 1 None None SUDS
22539601 2012 None None None None
21129503 2011 170 None 26 None
20031635 2009 80 41 39 None
19716085 2009 5 None 5 None
19114714 2009 None None None None
17053194 2006 None None None None
Literature, cohort, and gnomAD – 96 6 90 –
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 Y111C.
Neighbour residue Distance (Å) Observed variants
111 0 Y111C,
112 5
115 5 E115A, E115G,
177 5 S177F,
180 6
108 6 G108S,
178 6 A178T, A178del,
116 6
114 6
110 6 V110I,
181 6 R181C,
174 7 R174H, R174C, R174L,
179 8 G179S,
107 8 Q107H, Q107H,
113 8
184 9 Y184S, Y184C, Y184D, Y184H
193 9 F193L, F193L, F193L,
117 9 P117L,
244 9
173 9
175 10 L175I,
109 10 R109C, R109L,
243 10 R243H, R243C, R243P, R243S,
106 11
183 11 K183R,
176 11
190 11 R190W, R190Q, R190L,
182 11
122 11 C122Y,
170 12
118 12
196 12
105 12
171 12
126 12 H126D,
172 12 V172M, V172E,
199 13 S199A,
189 13 G189R, G189R, G189E,
119 13 G119R, G119V,
185 13 V185L, V185L, V185M, V185del,
198 13 I198V, I198T,
194 13 A194P, A194T,
104 14 T104A, T104I,
125 14
186 14 G186R, G186D,
245 14 G245V,
202 14 D202N, D202H,
121 15
242 15 D242N, D242Y,
192 15 R192C, R192H,