KCNQ1 Variant L262P

Summary of observed carriers, functional annotations, and structural context for KCNQ1 L262P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

54%

5/11 effective observations

Total carriers

1 LQT1 · 0 unaffected

Functional studies

Publications with functional data

L262P 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 (%)
-6.8	0.999	-5	0.978	56

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	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.

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 L262P.
Neighbour residue	Distance (Å)	Observed variants
259	7	R259C, R259H, R259L, R259G,
251	11	L251P, L251Q,
265	11	T265I,
339	12	F339del, F339S,
254	12	V254M, V254L, V254L,
250	12	L250H, L250P,
255	13
264	13
252	14	G252R,
354	14
266	14	L266P,
247	14	T247I,
253	14	S253A, S253P,
268	14	I268V, I268S,
335	14	F335L, F335L, F335L,
336	14	A336S,
345	14	G345R, G345R, G345A,
263	15
257	15	I257V,
342	15	L342F, L342P,
269	15	G269D, G269S, G269del,
334	15	V334A