KCNH2 Variant R531Del

Summary of observed carriers, functional annotations, and structural context for KCNH2 R531Del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

31%

3/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

R531Del has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

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 (%)
None None None None 80

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
24606995 2014 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
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 R531Del.
Neighbour residue Distance (Å) Observed variants
531 0 R531W, R531Del, R531Q,
504 5 A504V,
463 5 F463L, F463L, F463L,
528 6 R528W, R528X, R528P,
421 6 T421fsX, T421M,
530 6
418 6
529 7
534 7 R534C,
527 7
532 7
501 8 D501N, D501H, D501Y,
505 8 A505V,
417 8
459 8
460 8 D460fsX,
533 8
503 8
422 9 A422T,
414 9 I414fsX,
425 9
502 9 M502I, M502I, M502I,
420 9 Y420C,
500 10 I500Del,
466 10 D466E, D466E,
526 10
462 10 M462Ins,
506 10 I506V,
464 10 I464X,
419 10
456 10 D456Y,
535 11 V535M,
525 11 K525N, K525N,
415 11
467 11
507 11 P507S, P507L,
461 11
423 12
416 12
465 12
537 12 R537W,
424 12
426 12 P426H,
458 13
457 13 L457P,
498 13
413 13 L413P,
536 13 A536X,
538 13
524 13
499 13
497 13 W497L, W497X,
410 13 W410X,
411 14
563 14 W563G, W563C, W563C, W563X
508 14
470 14 N470D,
455 14
559 14 L559F, L559H,
428 14 S428fsX, S428X, S428L,
469 15
468 15 L468F, L468X, L468R,