KCNH2 Variant T421fsX

Summary of observed carriers, functional annotations, and structural context for KCNH2 T421fsX. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

%

NA/NA effective observations

Total carriers

3

3 LQT2 · 0 unaffected

Functional studies

2

Publications with functional data

T421fsX has not been reported in gnomAD. This residue resides in a None region for LQT2.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
None None None None

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 LQT2 Other Disease
7889573 1995 4 0 3
Literature, cohort, and gnomAD – 3 0 3 –
Variant features alone – 10 NA NA –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Functional assay results from published electrophysiology studies. Steady state (S.S.) and peak tail current are relative % to wildtype (100% being no different from wildtype). V1/2 activation and inactivation are the voltages at which half of the maximal current is reached, in mV. Recovery from inactivation and deactivation time are ratios of characteristic time constants with wildtype. HM indicates homomeric channels, HT indicates heteromeric channels.

Homomeric channel data

Published electrophysiology measurements (homomeric).
PubMed ID Cell Type S.S Peak (%WT) Peak Tail IKr (%WT) V1/2 Act. V1/2 Inact. Recov. Inact. Deactivation (%WT)
8700910 Xeno 0 None None None None
8995352 COS7 None None None None

Heteromeric channel data

Published electrophysiology measurements (heteromeric).
PubMed ID Cell Type S.S Peak (%WT) Peak Tail IKr (%WT) V1/2 Act. V1/2 Inact. Deactivation (%WT)
8700910 Xeno 57 0.0 None None
8995352 COS7 68 None None None