KCNH2 Variant R534P

Summary of observed carriers, functional annotations, and structural context for KCNH2 R534P. 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

R534P 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 3%. 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 (%)
-6.709 1.0 0 0.965 81

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 R534P.
Neighbour residue Distance (Å) Observed variants
534 0 R534C,
501 5 D501N, D501H, D501Y,
533 5
537 6 R537W,
535 7 V535M,
538 7
531 7 R531W, R531Del, R531Q,
466 7 D466E, D466E,
463 7 F463L, F463L, F463L,
414 7 I414fsX,
532 7
418 8
536 8 A536X,
530 8
497 8 W497L, W497X,
500 8 I500Del,
504 9 A504V,
470 9 N470D,
411 9
467 9
415 9
417 10
502 10 M502I, M502I, M502I,
498 10
410 10 W410X,
493 11 Y493H, Y493C, Y493F, Y493Ins,
505 11 A505V,
421 11 T421fsX, T421M,
503 11
542 11
462 11 M462Ins,
529 11
469 11
464 11 I464X,
465 11
539 12
407 12
413 12 L413P,
496 12
499 12
459 12
527 12
528 12 R528W, R528X, R528P,
419 12
541 13 R541C, R541H
416 13
460 13 D460fsX,
412 13 W412X,
468 13 L468F, L468X, L468R,
422 13 A422T,
471 13 F471X,
473 13 T473P,
540 14 D540fsX,
408 14
461 14
506 14 I506V,
420 14 Y420C,
492 15 H492Y,
409 15 V409M, V409L, V409L,