KCNH2 Variant L529Q

Summary of observed carriers, functional annotations, and structural context for KCNH2 L529Q. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

21%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

L529Q 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 23%. 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 (%)
-5.751 0.998 -2 0.944 69

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 L529Q.
Neighbour residue Distance (Å) Observed variants
529 0
530 5
527 5
526 6
422 6 A422T,
532 6
421 7 T421fsX, T421M,
531 7 R531W, R531Del, R531Q,
528 7 R528W, R528X, R528P,
425 7
563 8 W563G, W563C, W563C, W563X,
426 8 P426H,
418 9
533 9
504 9 A504V,
423 10
525 10 K525N, K525N,
503 10
559 11 L559F, L559H,
419 11
500 11 I500Del,
534 11 R534C,
420 11 Y420C,
524 11
429 12 A429P, A429V,
424 12
501 12 D501N, D501H, D501Y,
463 12 F463L, F463L, F463L,
523 12
562 12 H562P, H562R, H562Q, H562Q,
535 12 V535M,
428 12 S428fsX, S428X, S428L,
417 12
505 13 A505V,
566 13 C566S, C566R, C566G, C566S, C566F,
560 13 I560fsX, I560M,
522 13 G522E,
459 13
460 13 D460fsX,
502 13 M502I, M502I, M502I,
506 13 I506V,
536 13 A536X,
456 13 D456Y,
556 14
415 14
567 14 I567T, I567M
430 14
427 14 Y427H, Y427S, Y427C,
564 14 L564L,
414 14 I414fsX,
561 14 A561T, A561P, A561V,
558 15 A558P, A558E, A558V,
507 15 P507S, P507L,
555 15
537 15 R537W,
416 15
499 15