KCNQ1 Variant L266P

Summary of observed carriers, functional annotations, and structural context for KCNQ1 L266P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

85%

49/58 effective observations

Total carriers

48

45 LQT1 · 3 unaffected

Functional studies

0

Publications with functional data

L266P 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 (%)
-6.7 0.999 -4 0.941 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 4 None 4 None
27000522 2017 4 None 4 None
23631430 2013 7 None None None
23153844 2012 32 None 1 None
22949429 2012 5 None 5 None
21131640 2011 1 None 1 None
19841300 2009 5 None 5 None
19817925 2010 23 3 6 None
19716085 2009 30 None 30 None
19490272 2009 22 None 22 None
17470695 2007 15 None 15 None
14678125 2003 6 None 6 None
Literature, cohort, and gnomAD 48 3 45
Variant features alone 15 6 4

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 L266P.
Neighbour residue Distance (Å) Observed variants
263 6
339 11 F339del, F339S,
259 11 R259C, R259H, R259L, R259G,
260 12
334 12 V334A
335 12 F335L, F335L, F335L,
336 12 A336S,
274 12 I274V,
251 12 L251P, L251Q,
266 13 L266P,
265 13 T265I,
269 13 G269D, G269S, G269del,
347 13 L347P, L347R,
238 13 M238V, M238L, M238L,
242 14 D242N, D242Y,
268 14 I268V, I268S,
246 14
333 14
351 14 F351L, F351L, F351L, F351S,
241 14 V241F, V241I, V241G,
338 14 S338F,
247 14 T247I,
239 15
255 15
250 15 L250H, L250P,
130 15
310 15 V310I,