KCNQ1 Variant R594P

Summary of observed carriers, functional annotations, and structural context for KCNQ1 R594P. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

69%

7/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

R594P 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 (%)
-4.48 0.746 -2 0.884 72

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
19716085 2009 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 R594P.
Neighbour residue Distance (Å) Observed variants
594 0 R594Q, R594P,
593 4 N593S,
595 4 V595L, V595L
592 5
596 5 E596del, E596K,
591 7 R591H, R591C, R591L,
597 7
590 8 A590T,
598 8 K598R,
589 8 G589D, G589S,
599 8
588 9 I588F,
600 9 T600M,
587 10 T587M, T587R,
601 10
586 11 N586D,
602 11
585 11 S585N,
603 11
584 12 G584S,
604 12
583 13 R583H, R583C, R583G,
605 13
582 13
606 13
581 14
607 14 A607T,
580 14 S580G, S580N,
608 14
579 15
609 15