KCNQ1 Variant G325R

Summary of observed carriers, functional annotations, and structural context for KCNQ1 G325R. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

92%

29/32 effective observations

Total carriers

22

22 LQT1 · 0 unaffected

Functional studies

2

Publications with functional data

G325R 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 (%)
-7.45 1.0 -4 0.972 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
33382510 2021 1 None 1 None
32893267 2020 18 None 18 None
30758498 2019 9 None 5 None
26496715 2016 2 None 2 None
23631430 2013 1 None None None
23092362 2012 11 None None None
23000022 2012 1 None 1 None
22949429 2012 2 None 2 None
19841300 2009 2 None 2 None
19716085 2009 6 None 6 None
19490272 2009 8 None 8 None
17470695 2007 3 None 3 None
17192539 2006 2 None 2 None
14998624 2004 1 None 1 None
Literature, cohort, and gnomAD – 22 0 22 –
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 G325R.
Neighbour residue Distance (Å) Observed variants
325 0 G325R, G325R, G325E, G325W,
324 4
328 4 I328del,
322 5 T322M, T322A, T322K,
327 5 T327A, T327S, T327S,
320 6 P320H, P320A, P320S,
329 6 A329T,
283 6 A283G, A283T,
284 7 E284K,
323 7
321 8
330 8
279 8 F279I,
282 9 L282P,
331 9
332 10
287 11 A287E, A287T, A287S,
333 11
278 11 Y278H,
304 11 W304R, W304R,
285 12
286 12
305 13 W305S, W305L, W305C, W305C, W305R, W305R
308 13 V308F,
301 13
307 13 V307L, V307L,
318 14
302 14 A302V, A302E, A302T,
300 14 A300T, A300S,
306 14 G306V, G306R, G306R,
288 14
303 14 L303P,
326 14
334 14 V334A,
275 14 F275del,
289 14
317 14 D317N, D317G, D317Y,
272 15 G272D, G272S, G272V,
335 15 F335L, F335L, F335L,
296 15 F296S, F296L, F296L, F296L,