KCNQ1 Variant V334A

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V334A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

67%

7/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

V334A has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 6 individuals with LQT1 and 4 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-3.3 0.89 -2 0.931 70

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 LQT1 Other Disease
32893267 2020 1 None 1 None
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 4 6 –

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.

Previously observed variants near V334A.
Neighbour residue Distance (Å) Observed variants
270 11 F270S,
269 11 G269D, G269S, G269del,
339 11 F339del, F339S,
266 11 L266P,
273 12 L273F, L273V, L273R,
327 12 T327A, T327S, T327S,
306 12 G306V, G306R, G306R,
265 13 T265I,
272 13 G272D, G272S, G272V,
312 13 T312del, T312I,
336 13 A336S,
311 14 T311A, T311I,
255 14
325 14 G325R, G325R, G325E, G325W,
268 14 I268V, I268S,
332 14
334 14 V334A
313 14
326 14
333 14
341 14 A341V, A341E,
262 15 L262P, L262R, L262V,
276 15 S276del,
344 15 A344V, A344E,
271 15
274 15 I274V,