KCNH2 Variant T367S

Summary of observed carriers, functional annotations, and structural context for KCNH2 T367S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

9%

1/13 effective observations

Total carriers

3

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

T367S is present in 2 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 106% of WT with a standard error of 29%. 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 (%)
-2.865 0.609 1 0.707 5

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
14661677 2003 1 1
Literature, cohort, and gnomAD – 3 1 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 T367S.
Neighbour residue Distance (Å) Observed variants
367 0 T367S, T367S,
366 4 R366X, R366Q,
368 4 H368Y,
365 5 E365G,
369 5 N369K, N369K,
364 7 K364X,
370 7
363 8 I363X,
371 8
362 8
372 8
361 9
373 9
360 10
374 10
359 11 I359V,
375 11
358 11
376 11 Q376sp, Q376R,
357 12 E357D, E357D,
377 12
356 13 R356C, R356H,
378 13
355 13 D355G,
379 13 S379Y,
354 14
380 14 L380X,
353 14 T353S, T353S,
381 14
352 15
382 15 A382T