KCNQ1 Variant T144A

Summary of observed carriers, functional annotations, and structural context for KCNQ1 T144A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

60%

6/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

1

Publications with functional data

T144A has not been reported 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 (%)
-4.5 0.998 -2 0.904 64

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
19716085 2009 1 None 1 None
17470695 2007 7 None 7 None
17224687 2007 2 1 1 None
14678125 2003 1 None 1 None
Literature, cohort, and gnomAD – 1 0 1 –
Variant features alone – 15 5 5 –

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 T144A.
Neighbour residue Distance (Å) Observed variants
144 0 T144A,
143 4 S143F, S143P, S143Y,
145 5
141 5 V141M,
298 6 S298I, S298N,
140 6 S140G, S140R, S140R, S140R,
142 7
299 7
231 7 R231C, R231H, R231S,
146 7 E146K, E146G, E146Q,
297 8 G297S, G297D, G297R,
281 8 Y281C
300 8 A300T, A300S,
149 8
148 9
285 9
227 10
147 10 Q147R,
301 10
152 10
139 10
138 11
302 11 A302V, A302E, A302T,
153 11 T153M,
303 11 L303P,
228 11
137 11 L137F, L137P,
156 11
230 12
296 12 F296S, F296L, F296L, F296L,
234 12 Q234H, Q234H,
150 12 A150T,
278 12 Y278H,
282 12 L282P,
136 12
226 12 A226V,
229 12 G229D,
277 12 S277L, S277del, S277P, S277W,
294 13 V294M,
286 13
151 13
280 13 V280A, V280E,
235 14 I235N,
155 14
284 14 E284K,
154 14
222 14
283 14 A283G, A283T,
232 14
274 14 I274V,
225 14 S225L, S225del,
135 14
223 14
323 15
160 15 E160del, E160K, E160V,
287 15 A287E, A287T, A287S,
295 15
233 15 L233P,