KCNQ1 Variant V129I

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V129I. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

19%

2/15 effective observations

Total carriers

5

0 LQT1 · 5 unaffected

Functional studies

1

Publications with functional data

V129I is present in 4 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 2 individuals with LQT1 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.76 0.879 2 0.604 31

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
22949429 2012 1 1 None None
19841300 2009 1 1 None None
Literature, cohort, and gnomAD – 5 5 0 –
Variant features alone – 15 8 2 –

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 V129I.
Neighbour residue Distance (Å) Observed variants
129 0 V129I,
128 4 A128del,
132 5 I132L,
130 6
126 6 H126D,
125 6
131 6
133 6 V133I,
127 7 F127L, F127L, F127L,
167 8
166 8 F166V,
241 8 V241F, V241I, V241G,
124 9
134 9 L134P,
163 9
240 9 H240R, H240P,
170 9
237 10
123 10
135 10
238 11 M238V, M238L, M238L,
136 11
243 11 R243H, R243C, R243P, R243S,
114 11
122 11 C122Y,
113 11
159 12 M159del,
137 12 L137F, L137P,
174 12 R174H, R174C, R174L,
239 12
162 12 V162M,
164 12
202 13 D202N, D202H,
168 13 G168R, G168R, G168R, G168R,
242 13 D242N, D242Y,
121 13
234 13 Q234H, Q234H,
169 13 T169M, T169R,
117 13 P117L,
165 13 V165M,
160 13 E160del, E160K, E160V,
115 13 E115A, E115G,
120 14 W120C, W120C,
236 14 L236Q, L236R,
205 14 V205M,
138 14
235 14 I235N,
171 15
139 15
119 15 G119R, G119V,
198 15 I198V, I198T,
173 15
267 15 Y267C
206 15 V206L,