KCNQ1 Variant M159del

Summary of observed carriers, functional annotations, and structural context for KCNQ1 M159del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

72%

8/12 effective observations

Total carriers

2

2 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

M159del has not been reported in gnomAD. This residue resides in a NA region for LQT1.

Variant features alone are equivalent to phenotyping 6 individuals with LQT1 and 4 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
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
32893267 2020 2 None 2 None
Literature, cohort, and gnomAD – 2 0 2 –
Variant features alone – 15 4 6 –

Totals may differ from individual publications due to duplicate patients removed during curation.

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 M159del.
Neighbour residue Distance (Å) Observed variants
159 0 M159del,
156 5
160 5 E160del, E160K, E160V,
158 5
163 6
155 6
162 6 V162M,
136 6
161 7
139 8
132 8 I132L,
135 8
157 8 F157C,
154 8
152 9
164 9
133 10 V133I,
234 10 Q234H, Q234H,
153 11 T153M,
140 11 S140G, S140R, S140R, S140R,
237 11
166 11 F166V,
137 11 L137F, L137P,
167 11
165 11 V165M,
230 11
213 11
138 11
129 12 V129I,
209 12 S209P,
134 12 L134P,
143 12 S143F, S143P, S143Y,
151 12
131 13
142 13
233 13 L233P,
128 13 A128del,
149 14
231 14 R231C, R231H, R231S,
141 14 V141M,
226 14 A226V,
130 14
212 14
206 14 V206L
205 14 V205M,
216 15 G216R,
217 15
168 15 G168R, G168R, G168R, G168R,
150 15 A150T,
235 15 I235N,