KCNH2 Variant T319T
Summary of observed carriers, functional annotations, and structural context for KCNH2 T319T. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT2 penetrance
%
NA/NA effective observations
Total carriers
2
2 LQT2 · 0 unaffected
Functional studies
0
Publications with functional data
We have tested the trafficking efficiency of this variant: 125% of WT with a standard error of 10%. 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.
In silico 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
| Source | Year | Carriers | Unaffected | LQT2 | Other Disease |
|---|---|---|---|---|---|
| Japan Cohort | 2020 | 1 | 0 | 1 | |
| Literature, cohort, and gnomAD | – | 2 | 0 | 2 | – |
| Variant features alone | – | 10 | NA | NA | – |
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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 319 | 0 | T319T, |
| 318 | 4 | |
| 320 | 4 | S320X, S320W, S320L, |
| 317 | 5 | N317S, |
| 321 | 5 | D321Y, |
| 316 | 7 | |
| 322 | 7 | |
| 315 | 8 | |
| 323 | 8 | D323N, D323E, D323E, |
| 314 | 8 | G314S, |
| 324 | 8 | L324L, |
| 313 | 9 | |
| 325 | 9 | V325M, |
| 312 | 10 | R312C, R312Del, R312H, |
| 326 | 10 | R326C, R326fsX, R326H, |
| 311 | 11 | L311R, |
| 327 | 11 | Y327H, |
| 310 | 11 | P310X, P310L, |
| 328 | 11 | R328C, R328fsX, R328H, |
| 309 | 12 | H309Y, H309Q, H309Q, |
| 329 | 12 | |
| 308 | 13 | M308V, M308T, M308R, M308I, M308I, M308I, |
| 330 | 13 | I330V, |
| 307 | 13 | A307P, |
| 331 | 13 | S331N, S331T |
| 306 | 14 | G306W, |
| 332 | 14 | |
| 305 | 14 | |
| 333 | 14 | |
| 304 | 15 | S304R, S304R, S304R, |
| 334 | 15 | P334L, |