KCNQ1 Variant I588F

Summary of observed carriers, functional annotations, and structural context for KCNQ1 I588F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

51%

6/12 effective observations

Total carriers

2

1 LQT1 · 1 unaffected

Functional studies

0

Publications with functional data

I588F has not been reported 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 (%)
-2.94 0.992 -1 0.76 52

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
33614747 2021 1 None 1 None
27041150 2016 2 1 None None
Literature, cohort, and gnomAD 2 1 1
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 I588F.
Neighbour residue Distance (Å) Observed variants
588 0 I588F,
587 4 T587M, T587R,
589 4 G589D, G589S,
586 5 N586D,
590 5 A590T,
585 7 S585N,
591 7 R591H, R591C, R591L,
584 8 G584S,
592 8
583 8 R583H, R583C, R583G,
593 8 N593S,
582 9
594 9 R594Q, R594P,
581 10
595 10 V595L, V595L
580 11 S580G, S580N,
596 11 E596del, E596K,
579 11
597 11
578 12 E578K, E578V,
598 12 K598R,
577 13
599 13
576 13 V576I,
600 13 T600M,
575 14
601 14
574 14 I574V,
602 14
573 15 F573L, F573L, F573L,
603 15