KCNH2 Variant F348C

Summary of observed carriers, functional annotations, and structural context for KCNH2 F348C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

9%

0/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

F348C 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: 86% 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-1.408 0.99 -2 0.634 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 F348C.
Neighbour residue Distance (Å) Observed variants
348 0
347 4 P347S,
349 4
346 5 D346N, D346E, D346E, D346Y,
350 5
345 7 G345S,
351 7 S351L,
344 8
352 8
343 8 L343fsX,
353 8 T353S, T353S,
342 9 D342X, D342V, D342A,
354 9
341 10
355 10 D355G,
340 11 F340L, F340L, F340L,
356 11 R356C, R356H,
339 11
357 11 E357D, E357D,
338 12
358 12
337 13 T337S, T337X, T337S,
359 13 I359V,
336 13
360 13
335 14 Q335X,
361 14
334 14 P334L,
362 14
333 15
363 15 I363X,