KCNH2 Variant D411V

Summary of observed carriers, functional annotations, and structural context for KCNH2 D411V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

18%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

D411V 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: 0% of WT with a standard error of 0%. 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 (%)
-8.551 1.0 -3 0.929 26

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 D411V.
Neighbour residue Distance (Å) Observed variants
411 0
408 5
407 5
414 5 I414fsX,
410 5 W410X,
412 6 W412X,
541 6 R541H, R541C,
538 6
409 6 V409L, V409L, V409M,
542 7
413 7 L413P,
415 7
535 9 V535M,
534 9 R534C,
406 9
466 9 D466E, D466E,
537 10 R537W,
404 10
540 10 D540fsX,
416 10
417 10
405 10
469 11
539 11
418 11
470 11 N470D,
402 11 H402R,
3 11
536 11 A536X,
462 11 M462Ins,
463 12 F463L, F463L, F463L,
544 12 E544fsX, E544A,
473 12 T473P,
543 12 S543fsX,
465 13
532 13
533 13
401 13
545 13
403 13
419 13
400 13 I400N,
474 13 T474I,
548 13
552 13 L552S,
467 14
531 14 R531Q, R531Del, R531W,
501 14 D501H, D501Y, D501N,
551 15 F551L, F551L, F551L,
459 15
497 15 W497L, W497X,
468 15 L468X, L468R, L468F,