KCNH2 Variant D342Y

Summary of observed carriers, functional annotations, and structural context for KCNH2 D342Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

12%

1/11 effective observations

Total carriers

1

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

D342Y is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 11%. 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 (%)
-4.887 1.0 -4 0.82 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
Literature, cohort, and gnomAD – 1 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 D342Y.
Neighbour residue Distance (Å) Observed variants
342 0 D342V, D342X, D342A,
341 4
343 4 L343fsX,
340 5 F340L, F340L, F340L,
344 5
339 7
345 7 G345S,
338 8
346 8 D346N, D346E, D346Y, D346E,
337 8 T337S, T337X, T337S,
347 8 P347S,
336 9
348 9
335 10 Q335X,
349 10
334 11 P334L,
350 11
333 11
351 11 S351L,
332 12
352 12
331 13 S331N, S331T,
353 13 T353S, T353S,
330 13 I330V,
354 13
329 14
355 14 D355G,
328 14 R328fsX, R328H, R328C,
356 14 R356C, R356H,
327 15 Y327H,
357 15 E357D, E357D,