KCNH2 Variant V341M

Summary of observed carriers, functional annotations, and structural context for KCNH2 V341M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

8%

90% CI: 0.3% – 25.7%

0/11 effective observations

Total carriers

1

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

V341M 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: 81% of WT with a standard error of 28%. 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 (%)
-1.15 0.97 2 0.639 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 – 1 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 V341M.
Neighbour residue Distance (Å) Observed variants
341 0
340 4 F340L, F340L, F340L,
342 4 D342A, D342V, D342X,
339 5
343 5 L343fsX,
338 7
344 7
337 8 T337S, T337X, T337S,
345 8 G345S,
336 8
346 8 D346N, D346Y, D346E, D346E,
335 9 Q335X,
347 9 P347S,
334 10 P334L,
348 10
333 11
349 11
332 11
350 11
331 12 S331N, S331T
351 12 S351L,
330 13 I330V,
352 13
329 13
353 13 T353S, T353S,
328 14 R328C, R328fsX, R328H,
354 14
327 14 Y327H,
355 14 D355G,
326 15 R326C, R326fsX, R326H,
356 15 R356C, R356H,