KCNQ1 Variant Y278H

Summary of observed carriers, functional annotations, and structural context for KCNQ1 Y278H. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

74%

8/12 effective observations

Total carriers

2

2 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

Y278H 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 (%)
-4.74 0.999 -3 0.94 77

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
19490272 2009 2 None 2 None
17470695 2007 2 None 2 None
Literature, cohort, and gnomAD – 2 0 2 –
Variant features alone – 15 4 6 –

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 Y278H.
Neighbour residue Distance (Å) Observed variants
278 0 Y278H,
279 4 F279I,
282 6 L282P,
275 6 F275del,
232 6
277 6 S277L, S277del, S277P, S277W,
276 6 S276del,
280 7 V280A, V280E,
235 7 I235N,
281 7 Y281C
299 7
231 8 R231C, R231H, R231S,
274 8 I274V,
229 9 G229D,
228 9
283 9 A283G, A283T,
328 9 I328del,
302 9 A302V, A302E, A302T,
272 10 G272D, G272S, G272V,
236 10 L236Q, L236R,
332 10
303 10 L303P,
273 10 L273F, L273V, L273R,
233 10 L233P,
234 10 Q234H, Q234H,
285 11
230 11
284 11 E284K,
271 11
140 11 S140G, S140R, S140R, S140R,
137 12 L137F, L137P,
296 12 F296S, F296L, F296L, F296L,
306 12 G306V, G306R, G306R,
227 12
141 12 V141M,
324 12
144 12 T144A,
300 12 A300T, A300S,
225 12 S225L, S225del,
298 12 S298I, S298N,
238 12 M238V, M238L, M238L,
226 13 A226V,
239 13
301 13
237 13
297 13 G297S, G297D, G297R,
286 14
322 14 T322M, T322A, T322K,
305 14 W305S, W305L, W305C, W305C, W305R, W305R,
143 14 S143F, S143P, S143Y,
269 14 G269D, G269S, G269del,
335 14 F335L, F335L, F335L,
205 14 V205M,
224 14 T224M,
136 15
270 15 F270S,
336 15 A336S,