KCNH2 Variant A408T

Summary of observed carriers, functional annotations, and structural context for KCNH2 A408T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

13%

90% CI: 1.3% – 33.1%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

A408T has not been reported in gnomAD. This residue resides in a Non_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 (%)
-3.807 0.992 0 0.906 7

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 A408T.
Neighbour residue Distance (Å) Observed variants
408 0
409 4 V409M, V409L, V409L,
407 5
411 5
405 6
541 6 R541C, R541H,
404 6
412 7 W412X,
406 7
410 7 W410X,
542 9
402 9 H402R,
413 9 L413P,
403 10
3 10
414 10 I414fsX,
538 10
544 10 E544A, E544fsX
401 10
540 11 D540fsX,
545 11
415 11
400 12 I400N,
469 12
473 12 T473P,
466 13 D466E, D466E,
474 13 T474I,
543 13 S543fsX,
535 13 V535M,
539 13
470 13 N470D,
5 13
416 13
548 14
537 14 R537W,
534 14 R534C,
417 14
462 15 M462Ins,