KCNH2 Variant S515T

Summary of observed carriers, functional annotations, and structural context for KCNH2 S515T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

9%

0/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

S515T has not been reported in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 89% of WT with a standard error of 15%. 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 (%)
-1.236 0.236 1 0.656 8

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 S515T.
Neighbour residue Distance (Å) Observed variants
515 0
514 4 G514S,
516 4
513 5
517 5
512 7
518 7
511 8
519 8
510 8
520 8
509 9 D509N,
521 9
508 10
522 10 G522E,
507 11 P507S, P507L,
523 11
506 11 I506V,
524 11
505 12 A505V,
525 12 K525N, K525N,
504 13 A504V,
526 13
503 13
527 13
502 14 M502I, M502I, M502I,
528 14 R528W, R528X, R528P
501 14 D501N, D501H, D501Y,
529 14
500 15 I500Del,
530 15