KCNH2 Variant K407M

Summary of observed carriers, functional annotations, and structural context for KCNH2 K407M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

20%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

K407M has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of %. 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 (%)
-5.71 1.0 -2 0.941 43

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 K407M.
Neighbour residue Distance (Å) Observed variants
407 0
408 5
411 5
406 5
410 6 W410X,
404 6
409 7 V409M, V409L, V409L,
405 7
402 7 H402R,
469 8
473 8 T473P,
541 8 R541C, R541H,
401 8
400 8 I400N,
470 9 N470D,
538 9
466 9 D466E, D466E,
414 9 I414fsX,
474 9 T474I,
403 9
412 10 W412X,
413 10 L413P,
3 11
542 11
465 12
534 12 R534C,
537 12 R537W,
462 12 M462Ins,
415 12
399 12
540 13 D540fsX,
468 13 L468F, L468X, L468R,
472 13 R472C, R472X,
467 13
475 13 Y475C, Y475Del,
535 13 V535M,
471 13 F471X,
463 13 F463L, F463L, F463L,
5 14
476 14 V476I,
544 14 E544A, E544fsX
417 14
493 14 Y493H, Y493C, Y493F, Y493Ins,
539 14
489 15 I489F, I489I,
416 15
398 15 W398L, W398X,