KCNH2 Variant Y616S
Summary of observed carriers, functional annotations, and structural context for KCNH2 Y616S. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
34%
6/13 effective observations
Total carriers
3
3 LQT2 · 0 unaffected
Functional studies
0
Publications with functional data
We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 14%. 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.
Variant features alone are equivalent to phenotyping 3 individuals with LQT2 and 7 unaffected individuals.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT2 (%) |
|---|---|---|---|---|
| -8.536 | 0.989 | -2 | 0.946 | 89 |
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
| Source | Year | Carriers | Unaffected | LQT2 | Other Disease |
|---|---|---|---|---|---|
| Japan Cohort | 2020 | 3 | 0 | 3 | |
| Literature, cohort, and gnomAD | – | 3 | 0 | 3 | – |
| Variant features alone | – | 10 | 7 | 3 | – |
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. Note that some residues appear multiple times at different distances since the functional KV11.1 channel (protein product of KCNH2/hERG) is a homotetramer and occasionally the same residue from multiple subunits is present within the 15Å window.