KCNQ1 Variant M520R
Summary of observed carriers, functional annotations, and structural context for KCNQ1 M520R. Data combine curated literature, international cohorts, and gnomAD observations.
Estimated LQT1 penetrance
82%
11/14 effective observations
Total carriers
4
4 LQT1 · 0 unaffected
Functional studies
1
Publications with functional data
Variant features alone are equivalent to phenotyping 7 individuals with LQT1 and 3 unaffected individuals.
In silico predictors
| PROVEAN | PolyPhen-2 | BLAST-PSSM | REVEL | Penetrance Density LQT1 (%) |
|---|---|---|---|---|
| -4.4 | 0.907 | -2 | 0.959 | 83 |
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 |
|---|---|---|---|---|---|
| 32893267 | 2020 | 1 | None | 1 | None |
| 22949429 | 2012 | 1 | None | 1 | None |
| 19841300 | 2009 | 1 | None | 1 | None |
| 19716085 | 2009 | 3 | None | 3 | None |
| 17482572 | 2007 | 5 | None | 1 | None |
| 17470695 | 2007 | 3 | None | 3 | None |
| 17192539 | 2006 | 1 | None | 1 | None |
| Literature, cohort, and gnomAD | – | 4 | 0 | 4 | – |
| Variant features alone | – | 15 | 3 | 7 | – |
Totals may differ from individual publications due to duplicate patients removed during curation.
Functional data
Functional assay results from published electrophysiology studies. HM indicates homomeric channels, HT indicates heteromeric channels.
Homomeric channel data
| PubMed ID | Year | Study Type | Assay | Temperature | Cell Type | Result |
|---|
Heteromeric channel data
| PubMed ID | Year | Study Type | Assay | Temperature | Cell Type | Result |
|---|
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 |
|---|---|---|
| 520 | 0 | M520R, |
| 517 | 5 | I517T, |
| 516 | 5 | |
| 521 | 6 | |
| 523 | 6 | |
| 519 | 6 | R519H, R519C, |
| 524 | 8 | V524G, |
| 518 | 9 | R518Q, R518G, |
| 522 | 9 | Y522S, |
| 515 | 10 | |
| 513 | 10 | T513A, T513S, T513S |
| 514 | 10 | I514T, |
| 525 | 10 | A525T, A525V, |
| 377 | 10 | |
| 381 | 11 | C381Y, |
| 380 | 11 | R380S, R380S, R380G, |
| 512 | 11 | |
| 526 | 12 | K526Q, K526E, |
| 527 | 12 | |
| 528 | 13 | |
| 378 | 13 | A378T, |
| 373 | 13 | S373P, |
| 374 | 13 | L374H, L374F, |
| 384 | 14 | |
| 376 | 15 |