KCNH2 Variant L413V

Summary of observed carriers, functional annotations, and structural context for KCNH2 L413V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

28%

90% CI: 8.7% – 53.1%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

L413V has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 105% of WT with a standard error of 8%. 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 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-1.667 0.044 1 0.532 81

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 L413V.
Neighbour residue Distance (Å) Observed variants
413 0 L413P,
414 5 I414fsX,
410 5 W410X,
416 5
417 6
409 7 V409M, V409L, V409L,
415 7
411 7
412 7 W412X,
462 8 M462Ins,
418 9
408 9
407 10
459 10
463 10 F463L, F463L, F463L,
419 10
406 10
466 10 D466E, D466E,
542 11
420 12 Y420C,
465 12
534 12 R534C,
458 12
538 12
535 12 V535M,
541 12 R541C, R541H,
421 13 T421fsX, T421M,
461 13
531 13 R531W, R531Del, R531Q,
469 13
405 13
455 14
551 14 F551L, F551L, F551L,
460 14 D460fsX,
532 14
404 14
464 14 I464X,
552 15 L552S
470 15 N470D,
422 15 A422T,
456 15 D456Y,
548 15