KCNQ1 Variant R583C

Summary of observed carriers, functional annotations, and structural context for KCNQ1 R583C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

48%

7/16 effective observations

Total carriers

6

2 LQT1 · 4 unaffected

Functional studies

0

Publications with functional data

R583C is present in 4 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 (%)
-2.68 0.995 -2 0.825 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
32893267 2020 1 None 1 None
24606995 2014 1 None 1 None
Literature, cohort, and gnomAD 6 4 2
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 R583C.
Neighbour residue Distance (Å) Observed variants
583 0 R583H, R583C, R583G,
582 4
584 4 G584S,
581 5
585 5 S585N,
580 7 S580G, S580N,
586 7 N586D,
579 8
587 8 T587M, T587R,
578 8 E578K, E578V,
588 8 I588F,
577 9
589 9 G589D, G589S,
576 10 V576I,
590 10 A590T,
575 11
591 11 R591H, R591C, R591L,
574 11 I574V,
592 11
573 12 F573L, F573L, F573L,
593 12 N593S,
572 13
594 13 R594Q, R594P,
571 13 S571L, S571P,
595 13 V595L, V595L
570 14 P570L,
596 14 E596del, E596K,
569 14 K569E,
597 14
568 15 G568R, G568R, G568E,
598 15 K598R,