KCNH2 Variant N339K

Summary of observed carriers, functional annotations, and structural context for KCNH2 N339K. 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

N339K 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: 109% 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 (%)
-4.039 0.945 -1 0.749 2

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 N339K.
Neighbour residue Distance (Å) Observed variants
339 0
338 4
340 4 F340L, F340L, F340L,
337 5 T337X, T337S, T337S,
341 5
336 7
342 7 D342X, D342A, D342V,
335 8 Q335X,
343 8 L343fsX,
334 8 P334L,
344 8
333 9
345 9 G345S,
332 10
346 10 D346E, D346N, D346E, D346Y,
331 11 S331N, S331T,
347 11 P347S,
330 11 I330V,
348 11
329 12
349 12
328 13 R328H, R328C, R328fsX,
350 13
327 13 Y327H,
351 13 S351L,
326 14 R326H, R326fsX, R326C,
352 14
325 14 V325M,
353 14 T353S, T353S,
324 15 L324L,
354 15