KCNH2 Variant I330V

Summary of observed carriers, functional annotations, and structural context for KCNH2 I330V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

7%

90% CI: 0.2% – 22.4%

0/11 effective observations

Total carriers

1

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

I330V is present in 1 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 112% of WT with a standard error of 11%. 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 (%)
-0.519 0.093 2 0.505 3

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 – 1 1 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 I330V.
Neighbour residue Distance (Å) Observed variants
330 0 I330V,
329 4
331 4 S331N, S331T
328 5 R328C, R328fsX, R328H,
332 5
327 7 Y327H,
333 7
326 8 R326C, R326fsX, R326H,
334 8 P334L,
325 8 V325M,
335 8 Q335X,
324 9 L324L,
336 9
323 10 D323N, D323E, D323E,
337 10 T337S, T337X, T337S,
322 11
338 11
321 11 D321Y,
339 11
320 12 S320X, S320W, S320L,
340 12 F340L, F340L, F340L,
319 13 T319T,
341 13
318 13
342 13 D342A, D342V, D342X,
317 14 N317S,
343 14 L343fsX,
316 14
344 14
315 15
345 15 G345S,