We estimate the penetrance of LQTS for KCNH2 E1039X is %.
This variant was found in a total of 14 carriers in 2 papers or gnomAD (version 4),
4 had LQTS.
E1039X is not present in gnomAD.
We have tested the trafficking efficiency of this variant, 42% of WT
with a standard error of 29%; in our analysis we used SE < 20% as 'high quality'.
Approximately below 50% of WT is considered PS3 moderate and below 30% is PS3 strong.
E1039X 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).
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).