KCNH2 Variant S331T

Summary of observed carriers, functional annotations, and structural context for KCNH2 S331T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

8%

0/10 effective observations

Total carriers

0

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

S331T 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: 124% 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 (%)
-1.594 0.23 1 0.437 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 – 0 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 S331T.
Neighbour residue Distance (Å) Observed variants
331 0 S331N, S331T,
330 4 I330V,
332 4
329 5
333 5
328 7 R328H, R328C, R328fsX,
334 7 P334L,
327 8 Y327H,
335 8 Q335X,
326 8 R326fsX, R326H, R326C,
336 8
325 9 V325M,
337 9 T337S, T337X, T337S,
324 10 L324L,
338 10
323 11 D323E, D323N, D323E,
339 11
322 11
340 11 F340L, F340L, F340L,
321 12 D321Y,
341 12
320 13 S320L, S320W, S320X,
342 13 D342X, D342V, D342A,
319 13 T319T,
343 13 L343fsX,
318 14
344 14
317 14 N317S,
345 14 G345S,
316 15
346 15 D346N, D346E, D346E, D346Y,