KCNQ1 Variant S66F

Summary of observed carriers, functional annotations, and structural context for KCNQ1 S66F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

39%

4/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

S66F has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

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

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-2.01 0.085 -1 0.649 41

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 7 3 –

Totals may differ from individual publications due to duplicate patients removed during curation.

Functional data

Functional assay results from published electrophysiology studies. HM indicates homomeric channels, HT indicates heteromeric channels.

Homomeric channel data

Published electrophysiology measurements (homomeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

Heteromeric channel data

Published electrophysiology measurements (heteromeric).
PubMed ID Year Study Type Assay Temperature Cell Type Result

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 S66F.
Neighbour residue Distance (Å) Observed variants
66 0 S66Y, S66F
65 4 A65V,
67 4 P67L,
64 5 P64del,
68 5
63 7
69 7
62 8 A62V,
70 8
61 8 P61T,
71 8 A71T, A71S, A71V,
60 9
72 9
59 10
73 10 P73T, A73del, P73S,
58 11 A58P,
74 11
57 11 G57V,
75 11
56 12
76 12 A76T,
55 13 A55V,
77 13 S77F,
54 13 I54ins,
78 13 D78H,
53 14
79 14
52 14
80 14
51 15
81 15 P81L,