KCNQ1 Variant H258N

Summary of observed carriers, functional annotations, and structural context for KCNQ1 H258N. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

67%

7/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

H258N has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 6 individuals with LQT1 and 4 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-6.8 1.0 0 0.886 69

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
17192539 2006 1 None 1 None
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 4 6 –

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 H258N.
Neighbour residue Distance (Å) Observed variants
260 11
358 12 K358T,
259 12 R259C, R259H, R259L, R259G,
250 12 L250H, L250P,
254 12 V254M, V254L, V254L,
352 12
349 12 S349W,
265 13 T265I,
251 13 L251P, L251Q,
264 13
348 13
263 13
253 14 S253A, S253P
257 14 I257V,
353 14 L353P,
350 14 G350V, G350R, G350R, G350W,
252 14 G252R,
345 14 G345R, G345R, G345A,
255 15
355 15
351 15 F351L, F351L, F351L, F351S,