KCNQ1 Variant T169M

Summary of observed carriers, functional annotations, and structural context for KCNQ1 T169M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

9%

1/22 effective observations

Total carriers

12

0 LQT1 · 12 unaffected

Functional studies

1

Publications with functional data

T169M is present in 12 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 1 individuals with LQT1 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.5 0.501 1 0.507 12

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
Literature, cohort, and gnomAD – 12 12 0 –
Variant features alone – 15 9 1 –

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 T169M.
Neighbour residue Distance (Å) Observed variants
169 0 T169M, T169R,
168 4 G168R, G168R, G168R, G168R,
170 5
172 5 V172M, V172E,
166 6 F166V,
165 6 V165M,
173 6
167 7
171 8
164 9
174 9 R174H, R174C, R174L,
176 9
175 10 L175I,
206 10 V206L,
163 10
162 11 V162M,
114 11
202 12 D202N, D202H,
125 12
203 12 L203P,
177 13 S177F,
110 13 V110I,
161 13
129 13 V129I,
210 13 M210I, M210I, M210I,
113 13
205 13 V205M,
207 14 V207M, V207L, V207L, V207L, V207L, V207del
240 14 H240R, H240P,
209 14 S209P,
199 14 S199A,
126 14 H126D,
237 14
107 14 Q107H, Q107H,
115 14 E115A, E115G,
160 15 E160del, E160K, E160V,