KCNQ1 Variant R259H

Summary of observed carriers, functional annotations, and structural context for KCNQ1 R259H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

15%

2/16 effective observations

Total carriers

6

0 LQT1 · 6 unaffected

Functional studies

1

Publications with functional data

R259H is present in 5 alleles in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 2 individuals with LQT1 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-4.86 1.0 -2 0.974 45

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
26346102 2015 2 2 None None
16922724 2006 1 1 None None
Literature, cohort, and gnomAD – 6 6 0 –
Variant features alone – 15 8 2 –

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 R259H.
Neighbour residue Distance (Å) Observed variants
259 0 R259C, R259H, R259L, R259G,
256 5
263 6
266 11 L266P,
359 12 Q359del,
351 13 F351L, F351L, F351L, F351S,
250 13 L250H, L250P,
355 13
267 14 Y267C
251 14 L251P, L251Q,
261 14 E261K, E261D, E261D, E261G, E261Q,
354 14
254 14 V254M, V254L, V254L,
358 14 K358T,
247 15 T247I,
350 15 G350V, G350R, G350R, G350W,
260 15