KCNQ1 Variant S253P

Summary of observed carriers, functional annotations, and structural context for KCNQ1 S253P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

17%

1/11 effective observations

Total carriers

1

0 LQT1 · 1 unaffected

Functional studies

0

Publications with functional data

S253P is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 1 individuals with LQT1 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-4.86 1.0 -2 0.969 17

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 – 1 1 0 –
Variant features alone – 15 9 1 –

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 S253P.
Neighbour residue Distance (Å) Observed variants
253 0 S253A, S253P,
252 3 G252R,
254 4 V254M, V254L, V254L,
249 7 R249S, R249S,
246 10
245 11 G245V,
248 11 W248C, W248C, W248R, W248R
250 12 L250H, L250P,
261 12 E261K, E261D, E261D, E261G, E261Q,
351 12 F351L, F351L, F351L, F351S,
354 13
251 13 L251P, L251Q,
268 13 I268V, I268S,
355 13
260 13
258 13 H258P, H258N, H258R, H258Y,
339 14 F339del, F339S,
352 14
264 14
358 14 K358T,
262 14 L262P, L262R, L262V,
346 14
265 14 T265I,
242 14 D242N, D242Y,
257 15 I257V,
244 15
259 15 R259C, R259H, R259L, R259G,