KCNH2 Variant T152fsX Detail

We estimate the penetrance of LQTS for KCNH2 T152fsX is %. This variant was found in a total of 4 carriers in 7 papers or gnomAD (version 4), 4 had LQTS. T152fsX is not present in gnomAD. T152fsX has been functionally characterized in 1 papers. This residue is located in a None region for LQT2.

In Silico Data

PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density (%)
None None None None
PROVEAN scores less than -2 are considered deleterious. REVEL scores higher than 0.5 or 0.75 are considered likely pathogenic (higher sensitivity with the former cutoff, higher specificity with the latter cutoff). A PolyPhen-2 score of 0.85 or greater is considered likely pathogenic. BLAST-PSSM reflects the evolutionary conservation of residue substitutions, more negative numbers indicate fewer observations of the specific substitution than is expected. Penetrance density is our previously published method to calculate the average LQTS probability density in a shell of residues surrounding a residue of interest (Kroncke et al. 2019).

Reported Carrier Data

PubMed ID Year Carriers Unaffected LQT2 Other Disease
29622001 2018 24 0 0
Japan Cohort 2020 2 0 2
Japan Cohort 2020 2 1 1
Italy Cohort 2020 1 0 1
Italy Cohort 2020 4 1 3
23098067 2012 1 0 1
28049825 2016 3 0 3
LITERATURE, COHORT, AND GNOMAD: - 4 0 4 -
VARIANT FEATURES ALONE: - 10 NA NA -
Summary totals might not agree with the literature table because of duplicate patients, which were excluded from the total counts. We do not distinguish here between multiple missense codons. Missense variants are combined across degenerate codon substitutions since codon-level data were not consistently available for curation.

Functional Data Homozygously Collected

Steady state (S.S.) and peak tail current are relative % to wildtype (100% being no different from wildtype). V0.5 act/inact are the voltages at which half of the maximal current is reached during an activation and inactivation protocol, each is in units of mV and relative to wildtype. Recovery from inactivation (Rec. inact.) and deactivation time (Deactivation) are the ratio of characteristic time constants with wildtype (unitless).

PubMed ID Cell Type S.S Peak (%WT) Peak Tail IKr (%WT) V1/2 Act. V1/2 Inact. Recov. Inact. Deactivation (%WT)
28049825 CHO 0 None None None None

Functional Data Heterozygously Collected

Functional parameters are the same as defined above.

PubMed ID Cell Type S.S Peak (%WT) Peak Tail IKr (%WT) V1/2 Act. V1/2 Inact. Deactivation (%WT)
28049825 CHO 100 100 None None None