KCNH2 Variant N470Y

Summary of observed carriers, functional annotations, and structural context for KCNH2 N470Y. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

33%

3/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

N470Y has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

Variant features alone are equivalent to phenotyping 3 individuals with LQT2 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-7.213 1.0 -2 0.967 89

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 7 3 –

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 N470Y.
Neighbour residue Distance (Å) Observed variants
470 0 N470D,
469 5
471 5 F471X,
473 5 T473P,
466 5 D466E, D466E,
467 6
493 6 Y493H, Y493C, Y493F, Y493Ins,
468 7 L468F, L468X, L468R,
472 9 R472C, R472X,
489 9 I489F, I489I,
474 9 T474I,
407 9
465 9
498 9
534 9 R534C,
501 9 D501N, D501H, D501Y,
537 9 R537W,
400 10 I400N,
490 10 A490T, A490P,
475 10 Y475C, Y475Del,
538 10
410 10 W410X,
492 10 H492Y,
411 11
497 11 W497L, W497X,
464 11 I464X,
463 11 F463L, F463L, F463L,
402 11 H402R,
494 11 F494Del,
414 11 I414fsX,
496 12
502 12 M502I, M502I, M502I,
401 12
486 12
406 12
462 12 M462Ins,
399 13
491 13 V491I,
500 13 I500Del,
483 13 V483I,
505 13 A505V,
484 13
408 13
476 13 V476I,
533 13
404 13
504 13 A504V,
499 13
541 14 R541C, R541H
398 14 W398L, W398X,
487 14 G487S, G487R,
531 14 R531W, R531Del, R531Q,
535 14 V535M,
485 14 H485X,
536 15 A536X,
413 15 L413P,
461 15
403 15
503 15
409 15 V409M, V409L, V409L,
488 15 R488C, R488H,