KCNQ1 Variant S140R

Summary of observed carriers, functional annotations, and structural context for KCNQ1 S140R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

52%

5/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

S140R has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 4 individuals with LQT1 and 6 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-4.53 1.0 -3 0.729 49

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
26496715 2016 1 None 1 None
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 6 4 –

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 S140R.
Neighbour residue Distance (Å) Observed variants
140 0 S140G, S140R, S140R, S140R,
141 4 V141M,
143 5 S143F, S143P, S143Y,
137 6 L137F, L137P,
231 6 R231C, R231H, R231S,
139 6
142 6
136 6
144 6 T144A,
234 6 Q234H, Q234H,
138 6
299 7
156 8
230 8
145 9
152 9
135 9
235 9 I235N,
160 10 E160del, E160K, E160V,
149 10
148 10
300 10 A300T, A300S,
153 10 T153M,
133 10 V133I,
229 10 G229D,
134 11 L134P,
159 11 M159del,
298 11 S298I, S298N,
227 11
155 11
233 11 L233P,
281 11 Y281C
237 11
303 11 L303P,
226 11 A226V,
278 11 Y278H,
232 11
274 12 I274V,
228 12
146 12 E146K, E146G, E146Q,
154 12
238 12 M238V, M238L, M238L,
277 13 S277L, S277del, S277P, S277W,
302 13 A302V, A302E, A302T,
132 13 I132L,
147 13 Q147R,
297 13 G297S, G297D, G297R,
151 13
236 13 L236Q, L236R,
275 13 F275del,
157 13 F157C,
150 13 A150T,
301 13
163 14
225 14 S225L, S225del,
285 14
282 14 L282P,
222 14
209 14 S209P,
213 15
212 15
130 15
131 15
279 15 F279I,