KCNH2 Variant D355N

Summary of observed carriers, functional annotations, and structural context for KCNH2 D355N. 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

D355N 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: 112% of WT with a standard error of 44%. 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 (%)
-1.579 0.093 0 0.373 1

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 D355N.
Neighbour residue Distance (Å) Observed variants
355 0 D355G,
354 4
356 4 R356H, R356C,
353 5 T353S, T353S,
357 5 E357D, E357D,
352 7
358 7
351 8 S351L,
359 8 I359V,
350 8
360 8
349 9
361 9
348 10
362 10
347 11 P347S,
363 11 I363X,
346 11 D346Y, D346E, D346E, D346N,
364 11 K364X,
345 12 G345S,
365 12 E365G,
344 13
366 13 R366Q, R366X,
343 13 L343fsX,
367 13 T367S, T367S,
342 14 D342A, D342X, D342V,
368 14 H368Y,
341 14
369 14 N369K, N369K,
340 15 F340L, F340L, F340L
370 15