KCNH2 Variant T353S

Summary of observed carriers, functional annotations, and structural context for KCNH2 T353S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

5%

90% CI: 0.2% – 18.9%

0/15 effective observations

Total carriers

5

0 LQT2 · 3 unaffected

Functional studies

0

Publications with functional data

T353S is present in 4 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 100% of WT with a standard error of 14%. 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 (%)
-1.101 0.001 2 0.486 0

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
29396286 2018 1 1 >1 year post MI
Literature, cohort, and gnomAD – 5 3 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 T353S.
Neighbour residue Distance (Å) Observed variants
353 0 T353S, T353S,
352 4
354 4
351 5 S351L,
355 5 D355G,
350 7
356 7 R356C, R356H,
349 8
357 8 E357D, E357D,
348 8
358 8
347 9 P347S,
359 9 I359V,
346 10 D346N, D346Y, D346E, D346E,
360 10
345 11 G345S,
361 11
344 11
362 11
343 12 L343fsX,
363 12 I363X,
342 13 D342A, D342V, D342X,
364 13 K364X,
341 13
365 13 E365G,
340 14 F340L, F340L, F340L,
366 14 R366X, R366Q,
339 14
367 14 T367S, T367S,
338 15
368 15 H368Y