KCNH2 Variant Q335P

Summary of observed carriers, functional annotations, and structural context for KCNH2 Q335P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

8%

0/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

Q335P has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 131% of WT with a standard error of 17%. 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 (%)
-3.403 0.111 -2 0.809 27

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 Q335P.
Neighbour residue Distance (Å) Observed variants
335 0 Q335X,
334 4 P334L,
336 4
333 5
337 5 T337X, T337S, T337S,
332 7
338 7
331 8 S331N, S331T,
339 8
330 8 I330V,
340 8 F340L, F340L, F340L,
329 9
341 9
328 10 R328H, R328C, R328fsX,
342 10 D342X, D342A, D342V,
327 11 Y327H,
343 11 L343fsX,
326 11 R326H, R326fsX, R326C,
344 11
325 12 V325M,
345 12 G345S,
324 13 L324L,
346 13 D346E, D346N, D346E, D346Y,
323 13 D323E, D323N, D323E,
347 13 P347S,
322 14
348 14
321 14 D321Y,
349 14
320 15 S320W, S320L, S320X,
350 15