KCNQ1 Variant S338F

Summary of observed carriers, functional annotations, and structural context for KCNQ1 S338F. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

79%

12/16 effective observations

Total carriers

6

6 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

S338F 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 (%)
-5.67 1.0 -2 0.949 75

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 2 None 2 None
23291057 2013 4 None 4 None
Literature, cohort, and gnomAD – 6 0 6 –
Variant features alone – 15 4 6 –

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 S338F.
Neighbour residue Distance (Å) Observed variants
266 11 L266P,
341 12 A341V, A341E,
344 12 A344V, A344E,
345 13 G345R, G345R, G345A,
338 13 S338F,
252 13 G252R,
270 13 F270S,
337 13
312 14 T312del, T312I,
307 14 V307L, V307L
342 14 L342F, L342P,
263 14
343 14 P343S, P343L, P343R,
268 14 I268V, I268S,
348 15
258 15 H258P, H258N, H258R, H258Y,
264 15
261 15 E261K, E261D, E261D, E261G, E261Q,
351 15 F351L, F351L, F351L, F351S,