KCNH2 Variant P507R

Summary of observed carriers, functional annotations, and structural context for KCNH2 P507R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

13%

90% CI: 1.2% – 32.6%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

P507R has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 67% of WT with a standard error of 19%. 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 (%)
-8.407 1.0 -2 0.958 63

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 P507R.
Neighbour residue Distance (Å) Observed variants
507 0 P507S, P507L,
506 4 I506V,
508 5
505 6 A505V,
460 7 D460fsX,
504 8 A504V,
509 9 D509N,
528 9 R528W, R528X, R528P,
525 9 K525N, K525N,
503 9
464 9 I464X,
457 9 L457P,
524 10
510 10
527 10
502 10 M502I, M502I, M502I,
461 10
456 11 D456Y,
463 11 F463L, F463L, F463L,
531 11 R531W, R531Del, R531Q
459 11
526 13
522 13 G522E,
458 13
521 13
467 13
501 13 D501N, D501H, D501Y,
530 14
453 14
462 14 M462Ins,
465 14
425 14
421 14 T421fsX, T421M,
523 14
529 15
454 15
500 15 I500Del,