KCNH2 Variant L380P

Summary of observed carriers, functional annotations, and structural context for KCNH2 L380P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

13%

90% CI: 1.5% – 33.7%

1/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

L380P 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: 0% of WT with a standard error of 9%. 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 (%)
-6.662 0.999 -3 0.936 14

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 L380P.
Neighbour residue Distance (Å) Observed variants
380 0 L380X,
379 4 S379Y,
381 4
378 5
382 5 A382T,
377 7
383 7
376 8 Q376sp, Q376R,
384 8
375 8
385 8
374 9
386 9 P386X,
373 10
387 10
372 11
388 11
371 11
389 11
370 12
390 12
369 13 N369K, N369K,
391 13 Q391X,
368 13 H368Y,
392 13
367 14 T367S, T367S,
393 14 P393L,
366 14 R366X, R366Q,
394 14 R394C, R394H
365 15 E365G,
395 15