KCNQ1 Variant S225L

Summary of observed carriers, functional annotations, and structural context for KCNQ1 S225L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

64%

14/23 effective observations

Total carriers

13

9 LQT1 · 4 unaffected

Functional studies

3

Publications with functional data

S225L is present in 3 alleles 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 (%)
-5.7 0.994 0 0.873 63

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 15 None 15 None
30758498 2019 2 None None None
29688407 2018 1 1 None None
26496715 2016 6 None 6 None
24606995 2014 1 None 1 None
23153844 2012 22 None 1 None
22949429 2012 2 None 2 None
22885918 2012 1 None 1 None
19841300 2009 2 None 2 None
19716085 2009 8 None 8 None
19590188 2009 None None None None
19490272 2009 12 None 12 None
17470695 2007 13 None 13 None
17192539 2006 3 None 3 None
14678125 2003 2 None 2 None
Literature, cohort, and gnomAD – 13 4 9 –
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 S225L.
Neighbour residue Distance (Å) Observed variants
225 0 S225L, S225del,
226 4 A226V,
224 4 T224M,
229 5 G229D,
221 5
228 5
227 5
212 6
223 6
222 6
230 7
211 8
208 9 A208V,
231 9 R231C, R231H, R231S,
215 9 V215M, V215G, V215L, V215L,
219 9 G219E,
220 9 Q220K,
233 9 L233P,
209 10 S209P,
213 10
232 10
216 10 G216R,
282 11 L282P,
217 11
214 11 C214Y,
234 12 Q234H, Q234H,
210 12 M210I, M210I, M210I,
278 12 Y278H,
207 13 V207M, V207L, V207L, V207L, V207L, V207del,
205 13 V205M,
160 13 E160del, E160K, E160V,
218 13
157 13 F157C,
285 13
236 14 L236Q, L236R,
140 14 S140G, S140R, S140R, S140R,
204 14 I204M, I204F,
235 14 I235N,
281 14 Y281C
237 14
144 14 T144A,
206 14 V206L,
143 14 S143F, S143P, S143Y,
156 14
279 14 F279I,
153 14 T153M,
161 15