KCNQ1 Variant R293C

Summary of observed carriers, functional annotations, and structural context for KCNQ1 R293C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

53%

15/30 effective observations

Total carriers

20

10 LQT1 · 10 unaffected

Functional studies

0

Publications with functional data

R293C is present in 10 alleles in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 5 individuals with LQT1 and 5 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-4.1 0.969 -3 0.68 56

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
33876311 2021 1 0 1 None
32893267 2020 2 None 2 None
29197658 2018 5 None 5 None
28944242 2017 None None None None
19716085 2009 4 None 4 None
Literature, cohort, and gnomAD 20 10 10
Variant features alone 15 5 5

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 R293C.
Neighbour residue Distance (Å) Observed variants
298 11 S298I, S298N
321 12
288 12
319 13 V319L, V319L,
290 13 E290K,
294 13 V294M,
302 13 A302V, A302E, A302T,
300 14 A300T, A300S,
291 14
287 14 A287E, A287T, A287S,
320 14 P320H, P320A, P320S,
289 14