KCNQ1 Variant L353P

Summary of observed carriers, functional annotations, and structural context for KCNQ1 L353P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

88%

15/18 effective observations

Total carriers

8

8 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

L353P has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

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

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-6.62 0.996 -3 0.968 92

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 2 None 2 None
27041096 2016 2 None 2 None
22949429 2012 1 None 1 None
19841300 2009 1 None 1 None
19490272 2009 4 None 4 None
17470695 2007 4 None 4 None
Literature, cohort, and gnomAD 8 0 8
Variant features alone 15 3 7

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 L353P.
Neighbour residue Distance (Å) Observed variants
353 8 L353P,
352 9
349 9 S349W,
356 10
350 10 G350V, G350R, G350R, G350W,
348 11
355 12
357 12 Q357H, Q357H,
345 13 G345R, G345R, G345A,
354 13
351 13 F351L, F351L, F351L, F351S,
346 13
359 14 Q359del,
360 14 R360ins, R360G, R360M,
258 14 H258P, H258N, H258R, H258Y,
347 14 L347P, L347R