KCNQ1 Variant L175I

Summary of observed carriers, functional annotations, and structural context for KCNQ1 L175I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

28%

3/13 effective observations

Total carriers

3

0 LQT1 · 3 unaffected

Functional studies

0

Publications with functional data

L175I is present in 3 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 3 individuals with LQT1 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-1.84 0.78 2 0.708 37

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
Literature, cohort, and gnomAD – 3 3 0 –
Variant features alone – 15 7 3 –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 L175I.
Neighbour residue Distance (Å) Observed variants
175 0 L175I,
172 5 V172M, V172E,
190 5 R190W, R190Q, R190L,
171 5
176 6
193 6 F193L, F193L, F193L,
173 6
177 6 S177F,
174 6 R174H, R174C, R174L,
178 7 A178T, A178del,
194 8 A194P, A194T,
199 9 S199A,
179 9 G179S,
189 9 G189R, G189R, G189E,
191 9
170 9
184 9 Y184S, Y184C, Y184D, Y184H
168 10 G168R, G168R, G168R, G168R,
111 10 Y111C,
186 10 G186R, G186D,
169 10 T169M, T169R,
187 10 L187P, L187F,
114 10
203 10 L203P,
115 11 E115A, E115G,
107 11 Q107H, Q107H,
202 11 D202N, D202H,
110 11 V110I,
180 11
196 12
185 12 V185L, V185L, V185M, V185del,
181 12 R181C,
200 12
195 12 R195Q, R195W,
198 12 I198V, I198T,
192 13 R192C, R192H,
188 13 W188C, W188C, W188G, W188S,
108 13 G108S,
206 13 V206L,
183 13 K183R,
243 13 R243H, R243C, R243P, R243S,
167 13
197 14 P197L,
112 14
201 14 I201del,
113 14
166 14 F166V,
244 14
182 15
240 15 H240R, H240P,
106 15
204 15 I204M, I204F,