KCNH2 Variant T526S

Summary of observed carriers, functional annotations, and structural context for KCNH2 T526S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

14%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

T526S has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 65% of WT with a standard error of 9%. 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 1 individuals with LQT2 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-3.826 0.756 1 0.868 37

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 9 1 –

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 T526S.
Neighbour residue Distance (Å) Observed variants
526 0
527 4
529 6
525 6 K525N, K525N,
523 6
524 6
528 6 R528P, R528W, R528X,
425 7
522 8 G522E,
426 8 P426H,
429 8 A429V, A429P,
530 8
421 10 T421fsX, T421M,
531 10 R531W, R531Q, R531Del,
428 10 S428fsX, S428L, S428X,
504 10 A504V,
503 10
422 10 A422T,
430 11
563 11 W563X, W563G, W563C, W563C
521 11
508 11
506 12 I506V,
532 12
566 12 C566F, C566S, C566G, C566R, C566S,
423 12
507 13 P507L, P507S,
424 13
505 13 A505V,
567 13 I567T, I567M,
500 13 I500Del,
520 13
456 13 D456Y,
427 13 Y427H, Y427C, Y427S,
460 13 D460fsX,
420 13 Y420C,
432 13
418 14
533 14
502 14 M502I, M502I, M502I,
562 14 H562R, H562Q, H562P, H562Q,
431 14 F431L, F431L, F431L,
501 14 D501H, D501N, D501Y,
463 14 F463L, F463L, F463L,
570 14
559 15 L559F, L559H,
459 15