KCNQ1 Variant V280A

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V280A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

82%

9/12 effective observations

Total carriers

2

2 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

V280A has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 7 individuals with LQT1 and 3 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-3.89 0.994 1 0.933 88

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
17192539 2006 1 None 1 None
Literature, cohort, and gnomAD – 2 0 2 –
Variant features alone – 15 3 7 –

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 V280A.
Neighbour residue Distance (Å) Observed variants
280 0 V280A, V280E,
277 5 S277L, S277del, S277P, S277W,
284 6 E284K,
283 6 A283G, A283T,
276 6 S276del,
279 6 F279I,
281 6 Y281C
296 6 F296S, F296L, F296L, F296L,
282 7 L282P,
278 7 Y278H,
299 8
285 9
332 9
295 10
287 10 A287E, A287T, A287S,
275 10 F275del,
297 10 G297S, G297D, G297R,
274 11 I274V,
286 11
272 12 G272D, G272S, G272V,
302 12 A302V, A302E, A302T,
231 12 R231C, R231H, R231S,
305 12 W305S, W305L, W305C, W305C, W305R, W305R,
294 12 V294M,
304 12 W304R, W304R,
228 13
306 13 G306V, G306R, G306R,
232 13
303 13 L303P,
301 13
318 13
144 13 T144A,
235 13 I235N,
308 13 V308F,
307 14 V307L, V307L,
288 14
300 14 A300T, A300S,
141 14 V141M,
326 14
336 14 A336S,
289 14
335 14 F335L, F335L, F335L,
229 15 G229D,
317 15 D317N, D317G, D317Y,
298 15 S298I, S298N,
273 15 L273F, L273V, L273R,
320 15 P320H, P320A, P320S,
271 15