KCNH2 Variant P347T

Summary of observed carriers, functional annotations, and structural context for KCNH2 P347T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

8%

90% CI: 0.2% – 24.4%

0/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

P347T has not been reported in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 126% 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-2.295 0.23 -1 0.529 1

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 10 0 –

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 P347T.
Neighbour residue Distance (Å) Observed variants
347 0 P347S,
346 4 D346N, D346Y, D346E, D346E,
348 4
345 5 G345S,
349 5
344 7
350 7
343 8 L343fsX,
351 8 S351L,
342 8 D342A, D342V, D342X,
352 8
341 9
353 9 T353S, T353S,
340 10 F340L, F340L, F340L,
354 10
339 11
355 11 D355G,
338 11
356 11 R356C, R356H,
337 12 T337S, T337X, T337S,
357 12 E357D, E357D,
336 13
358 13
335 13 Q335X,
359 13 I359V
334 14 P334L,
360 14
333 14
361 14
332 15
362 15