KCNQ1 Variant Y281C

Summary of observed carriers, functional annotations, and structural context for KCNQ1 Y281C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

72%

7/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

Y281C 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 (%)
-8.75 0.999 -4 0.981 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 1 None 1 None
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.

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 Y281C.
Neighbour residue Distance (Å) Observed variants
281 0 Y281C
285 5
299 6
282 6 L282P,
297 6 G297S, G297D, G297R,
296 6 F296S, F296L, F296L, F296L,
280 6 V280A, V280E,
298 6 S298I, S298N,
302 6 A302V, A302E, A302T,
284 7 E284K,
283 7 A283G, A283T,
278 7 Y278H,
144 8 T144A,
277 8 S277L, S277del, S277P, S277W,
231 8 R231C, R231H, R231S,
301 8
286 8
300 8 A300T, A300S,
303 9 L303P,
228 9
279 9 F279I,
287 9 A287E, A287T, A287S,
294 10 V294M,
141 10 V141M,
295 10
276 10 S276del,
227 11
145 11
140 11 S140G, S140R, S140R, S140R,
318 11
143 11 S143F, S143P, S143Y,
229 12 G229D,
305 12 W305S, W305L, W305C, W305C, W305R, W305R,
274 12 I274V,
232 12
328 12 I328del,
306 12 G306V, G306R, G306R,
275 12 F275del,
288 13
235 13 I235N,
146 13 E146K, E146G, E146Q,
273 13 L273F, L273V, L273R,
142 13
230 13
234 14 Q234H, Q234H,
293 14 R293C, R293H,
226 14 A226V,
137 14 L137F, L137P,
225 14 S225L, S225del,
289 14
224 15 T224M,
332 15
325 15 G325R, G325R, G325E, G325W,
322 15 T322M, T322A, T322K,
320 15 P320H, P320A, P320S,