KCNQ1 Variant I274V

Summary of observed carriers, functional annotations, and structural context for KCNQ1 I274V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

11%

6/60 effective observations

Total carriers

50

1 LQT1 · 49 unaffected

Functional studies

0

Publications with functional data

I274V is present in 49 alleles in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 5 individuals with LQT1 and 5 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.97 0.894 1 0.846 49

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
29197658 2018 1 None 1 None
19716085 2009 1 None 1 None
19490272 2009 1 None 1 None
18222468 2008 None None None None
17470695 2007 1 None 1 None
17210839 2007 1 None None None
Literature, cohort, and gnomAD – 50 49 1 –
Variant features alone – 15 5 5 –

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 I274V.
Neighbour residue Distance (Å) Observed variants
274 0 I274V,
273 4 L273F, L273V, L273R,
275 5 F275del,
272 5 G272D, G272S, G272V,
271 5
277 6 S277L, S277del, S277P, S277W,
235 6 I235N,
276 7 S276del,
303 7 L303P,
270 7 F270S,
238 8 M238V, M238L, M238L,
278 8 Y278H,
299 8
269 8 G269D, G269S, G269del,
137 9 L137F, L137P,
306 9 G306V, G306R, G306R,
279 9 F279I,
302 9 A302V, A302E, A302T,
267 10 Y267C,
236 10 L236Q, L236R,
232 10
239 10
268 10 I268V, I268S,
234 11 Q234H, Q234H,
280 11 V280A, V280E,
300 11 A300T, A300S,
310 11 V310I,
141 11 V141M,
134 11 L134P,
140 12 S140G, S140R, S140R, S140R,
231 12 R231C, R231H, R231S,
340 12 F340del, F340L, F340L, F340L, F340S,
281 12 Y281C
138 12
133 12 V133I,
266 12 L266P,
237 13
339 13 F339del, F339S,
233 13 L233P,
130 13
282 13 L282P,
136 13
305 13 W305S, W305L, W305C, W305C, W305R, W305R,
301 13
298 14 S298I, S298N,
229 14 G229D,
240 14 H240R, H240P,
241 14 V241F, V241I, V241G,
248 14 W248C, W248C, W248R, W248R,
144 14 T144A,
330 14
265 14 T265I,
296 14 F296S, F296L, F296L, F296L,
135 15
230 15
331 15