KCNH2 Variant W410C

Summary of observed carriers, functional annotations, and structural context for KCNH2 W410C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

24%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

W410C has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 0%. 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 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-12.372 1.0 -3 0.967 44

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

Observed carriers by publication or cohort.
Source Year Carriers Unaffected LQT2 Other Disease
Literature, cohort, and gnomAD – 0 0 0 –
Variant features alone – 10 8 2 –

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.

Previously observed variants near W410C.
Neighbour residue Distance (Å) Observed variants
410 0 W410X,
413 5 L413P,
411 5
414 6 I414fsX,
407 6
409 6 V409M, V409L, V409L,
406 6
466 7 D466E, D466E,
462 7 M462Ins,
408 7
469 8
465 8
412 9 W412X,
417 9
463 10 F463L, F463L, F463L,
415 10
470 10 N470D,
405 10
416 10
534 10 R534C,
538 11
404 11
541 11 R541C, R541H
473 11 T473P,
467 12
400 12 I400N,
418 12
468 12 L468F, L468X, L468R,
542 12
459 12
461 12
464 12 I464X,
535 13 V535M,
401 13
402 13 H402R,
537 13 R537W,
458 13
531 13 R531W, R531Del, R531Q,
474 14 T474I,
501 14 D501N, D501H, D501Y,
419 14
460 14 D460fsX,
471 14 F471X,
472 15 R472C, R472X,
403 15