KCNQ1 Variant P320A

Summary of observed carriers, functional annotations, and structural context for KCNQ1 P320A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

74%

8/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

P320A 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 (%)
-7.35 1.0 2 0.931 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
32893267 2020 1 None 1 None
19540844 2010 None None None None
17192539 2006 2 None 2 None
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 3 7 –

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 P320A.
Neighbour residue Distance (Å) Observed variants
328 9 I328del,
283 9 A283G, A283T,
324 9
326 9
304 9 W304R, W304R,
323 10
325 11 G325R, G325R, G325E, G325W,
322 11 T322M, T322A, T322K,
318 12
305 12 W305S, W305L, W305C, W305C, W305R, W305R,
301 12
295 12
319 12 V319L, V319L,
282 12 L282P,
279 12 F279I,
306 13 G306V, G306R, G306R,
296 13 F296S, F296L, F296L, F296L,
332 13
320 13 P320H, P320A, P320S,
331 13
302 13 A302V, A302E, A302T,
307 13 V307L, V307L,
285 13
286 13
315 13 Y315C, Y315S, Y315N, Y315H, Y315F
327 13 T327A, T327S, T327S,
330 13
300 14 A300T, A300S,
314 14 G314S, G314D, G314C, G314del,
316 14 G316E, G316R, G316R, G316V,
303 14 L303P,
309 14 T309I, T309R,
278 14 Y278H,
293 14 R293C, R293H,
290 14 E290K,
280 15 V280A, V280E,
313 15
317 15 D317N, D317G, D317Y,