KCNQ1 Variant W305C

Summary of observed carriers, functional annotations, and structural context for KCNQ1 W305C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

79%

10/13 effective observations

Total carriers

3 LQT1 · 0 unaffected

Functional studies

Publications with functional data

W305C has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 7 individuals with LQT1 and 3 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN	PolyPhen-2	BLAST-PSSM	REVEL	Penetrance Density LQT1 (%)
-12.65	1.0	0	0.973	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
19490272	2009	3	None	3	None
Literature, cohort, and gnomAD	–	3	0	3	–
Variant features alone	–	15	3	7	–

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 W305C.
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,