KCNH2 Variant I467Ins

Summary of observed carriers, functional annotations, and structural context for KCNH2 I467Ins. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

20%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

I467Ins has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

Variant features alone are equivalent to phenotyping 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
None None None None 64

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 8 2 –

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 I467Ins.
Neighbour residue Distance (Å) Observed variants
467 0
468 5 L468F, L468X, L468R,
466 5 D466E, D466E,
470 6 N470D,
464 6 I464X,
465 6
471 6 F471X,
469 7
498 7
501 7 D501N, D501H, D501Y,
493 7 Y493H, Y493C, Y493F, Y493Ins,
502 8 M502I, M502I, M502I,
463 8 F463L, F463L, F463L,
505 8 A505V,
534 9 R534C,
504 9 A504V,
462 10 M462Ins,
473 10 T473P,
461 11
472 11 R472C, R472X,
494 11 F494Del,
503 11
531 11 R531W, R531Del, R531Q,
500 11 I500Del,
506 11 I506V,
410 12 W410X,
490 12 A490T, A490P,
499 12
460 12 D460fsX,
414 12 I414fsX,
537 12 R537W
497 12 W497L, W497X,
489 12 I489F, I489I,
496 13
407 13
459 13
538 13
507 13 P507S, P507L,
533 13
530 13
411 14
492 14 H492Y,
400 14 I400N,
417 14
474 14 T474I,
486 14
528 15 R528W, R528X, R528P,
491 15 V491I,
418 15