KCNH2 Variant S517T

Summary of observed carriers, functional annotations, and structural context for KCNH2 S517T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

9%

90% CI: 0.4% – 26.5%

0/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

S517T 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: 133% of WT with a standard error of 21%. 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-1.997 0.236 1 0.653 13

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 10 0 –

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 S517T.
Neighbour residue Distance (Å) Observed variants
517 0
516 4
518 4
515 5
519 5
514 7 G514S,
520 7
513 8
521 8
512 8
522 8 G522E,
511 9
523 9
510 10
524 10
509 11 D509N,
525 11 K525N, K525N,
508 11
526 11
507 12 P507S, P507L,
527 12
506 13 I506V,
528 13 R528W, R528X, R528P,
505 13 A505V,
529 13
504 14 A504V,
530 14
503 14
531 14 R531W, R531Del, R531Q
502 15 M502I, M502I, M502I,
532 15