KCNH2 Variant L550P

Summary of observed carriers, functional annotations, and structural context for KCNH2 L550P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

13%

90% CI: 1.3% – 32.9%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

L550P has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 38% of WT with a standard error of 15%. 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 (%)
-6.709 1.0 -1 0.96 15

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 L550P.
Neighbour residue Distance (Å) Observed variants
550 0
549 5 V549M,
547 5 A547T,
553 6 L553V,
548 6
551 6 F551L, F551L, F551L,
554 6
659 6
662 7
552 7 L552S,
546 7
663 8
555 9
650 9 L650X,
658 9
666 10
655 10
656 10 F656L, F656L, F656L,
660 10 S660L,
661 10 A661V,
556 10
665 11 R665Q,
543 11 S543fsX,
657 11 G657S, G657V,
557 11
545 11
654 12
667 12 Y667X,
646 12
649 12
653 12
664 13 Q664X,
542 13
558 13 A558P, A558E, A558V,
647 13
654 13
651 13 M651K,
544 14 E544A, E544fsX,
412 14 W412X,
539 14
415 14
648 14 G648A,
674 14 H674Y, H674fsX
651 14 M651K,
559 14 L559F, L559H,
652 15 Y652X,