KCNQ1 Variant W305S

Summary of observed carriers, functional annotations, and structural context for KCNQ1 W305S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

51%

9/19 effective observations

Total carriers

9

1 LQT1 · 8 unaffected

Functional studies

1

Publications with functional data

W305S is present in 1 alleles in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 8 individuals with LQT1 and 2 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-13.62 1.0 -4 0.949 83

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 3 None 3 None
23153844 2012 16 None 1 None
19716085 2009 1 None 1 None
19490272 2009 12 None 12 None
9781056 1998 7 7 None None
Literature, cohort, and gnomAD – 9 8 1 –
Variant features alone – 15 2 8 –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Functional assay results from published electrophysiology studies. HM indicates homomeric channels, HT indicates heteromeric channels.

Homomeric channel data

Published electrophysiology measurements (homomeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

Heteromeric channel data

Published electrophysiology measurements (heteromeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

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 W305S.
Neighbour residue Distance (Å) Observed variants
326 11
314 12 G314S, G314D, G314C, G314del,
281 12 Y281C,
330 12
316 13 G316E, G316R, G316R, G316V,
325 13 G325R, G325R, G325E, G325W,
274 13 I274V,
272 14 G272D, G272S, G272V,
315 14 Y315C, Y315S, Y315N, Y315H, Y315F
319 14 V319L, V319L,
313 14
327 14 T327A, T327S, T327S,
278 14 Y278H,
328 14 I328del,
322 14 T322M, T322A, T322K,
312 14 T312del, T312I,
284 15 E284K,
282 15 L282P,
309 15 T309I, T309R,