KCNQ1 Variant F296L

Summary of observed carriers, functional annotations, and structural context for KCNQ1 F296L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

36%

3/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

F296L has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 2 individuals with LQT1 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-5.74 0.995 -1 0.806 33

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
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 8 2 –

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 F296L.
Neighbour residue Distance (Å) Observed variants
297 6 G297S, G297D, G297R,
281 6 Y281C
294 7 V294M,
287 7 A287E, A287T, A287S,
285 8
283 8 A283G, A283T,
299 9
277 9 S277L, S277del, S277P, S277W,
286 10
282 10 L282P,
276 12 S276del,
144 12 T144A,
278 12 Y278H,
279 12 F279I,
320 12 P320H, P320A, P320S,
321 12
292 12 G292D,
326 13
145 13
141 13 V141M,
304 13 W304R, W304R,
322 14 T322M, T322A, T322K,
231 14 R231C, R231H, R231S,
273 14 L273F, L273V, L273R,
284 14 E284K,
325 14 G325R, G325R, G325E, G325W,
274 14 I274V,
301 15
228 15
296 15 F296S, F296L, F296L, F296L,