KCNQ1 Variant T224M
Summary of observed carriers, functional annotations, and structural context for KCNQ1 T224M. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT1 penetrance
39%
39/100 effective observations
Total carriers
90
35 LQT1 · 55 unaffected
Functional studies
0
Publications with functional data
Variant features alone are equivalent to phenotyping 4 individuals with LQT1 and 6 unaffected individuals.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT1 (%) |
|---|---|---|---|---|
| -4.67 | 1.0 | -1 | 0.948 | 45 |
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 | LQT1 | Other Disease |
|---|---|---|---|---|---|
| 33141630 | 2020 | 88 | 54 | 34 | None |
| 32470535 | 2020 | None | None | None | None |
| Literature, cohort, and gnomAD | – | 90 | 55 | 35 | – |
| Variant features alone | – | 15 | 6 | 4 | – |
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.
| Neighbour residue | Distance (Å) | Observed variants |
|---|---|---|
| 224 | 0 | T224M, |
| 223 | 4 | |
| 225 | 4 | S225L, S225del, |
| 221 | 5 | |
| 228 | 6 | |
| 227 | 6 | |
| 220 | 6 | Q220K, |
| 226 | 7 | A226V, |
| 222 | 7 | |
| 219 | 8 | G219E, |
| 229 | 9 | G229D, |
| 212 | 9 | |
| 215 | 10 | V215M, V215G, V215L, V215L, |
| 230 | 11 | |
| 211 | 11 | |
| 216 | 11 | G216R, |
| 231 | 11 | R231C, R231H, R231S, |
| 282 | 12 | L282P, |
| 217 | 12 | |
| 208 | 12 | A208V, |
| 285 | 13 | |
| 218 | 13 | |
| 213 | 13 | |
| 232 | 13 | |
| 286 | 13 | |
| 233 | 14 | L233P, |
| 209 | 14 | S209P, |
| 214 | 14 | C214Y, |
| 278 | 14 | Y278H, |
| 283 | 15 | A283G, A283T, |
| 281 | 15 | Y281C |