KCNH2 Variant D383A

Summary of observed carriers, functional annotations, and structural context for KCNH2 D383A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

11%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

D383A has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

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 (%)
-7.447 0.985 -2 0.883 39

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 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 D383A.
Neighbour residue Distance (Å) Observed variants
383 0
382 4 A382T,
384 4
381 5
385 5
380 7 L380X,
386 7 P386X,
379 8 S379Y,
387 8
378 8
388 8
377 9
389 9
376 10 Q376sp, Q376R,
390 10
375 11
391 11 Q391X,
374 11
392 11
373 12
393 12 P393L,
372 13
394 13 R394C, R394H,
371 13
395 13
370 14
396 14
369 14 N369K, N369K,
397 14 R397X, R397H,
368 15 H368Y,
398 15 W398L, W398X