KCNH2 Variant A536T

Summary of observed carriers, functional annotations, and structural context for KCNH2 A536T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

12%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

A536T has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 117% of WT with a standard error of 18%. 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 (%)
-3.834 0.065 0 0.837 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 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 A536T.
Neighbour residue Distance (Å) Observed variants
536 0 A536X,
535 4 V535M,
539 5
537 5 R537W,
533 6
538 6
532 7
534 8 R534C,
542 8
497 9 W497L, W497X,
540 9 D540fsX,
415 11
543 11 S543fsX,
552 11 L552S,
541 11 R541C, R541H,
418 11
530 11
411 11
501 12 D501N, D501H, D501Y,
500 12 I500Del,
414 12 I414fsX,
556 13
531 13 R531W, R531Del, R531Q,
496 13
412 13 W412X,
529 13
549 13 V549M,
553 13 L553V,
667 13 Y667X
3 14
419 14
670 14
555 14
466 14 D466E, D466E,
544 14 E544A, E544fsX,
470 15 N470D,
548 15
422 15 A422T,
463 15 F463L, F463L, F463L,
417 15
493 15 Y493H, Y493C, Y493F, Y493Ins,
421 15 T421fsX, T421M,