KCNQ1 Variant V165M

Summary of observed carriers, functional annotations, and structural context for KCNQ1 V165M. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

11%

1/16 effective observations

Total carriers

6

0 LQT1 · 6 unaffected

Functional studies

0

Publications with functional data

V165M is present in 6 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 (%)
-2.13 0.981 1 0.897 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
24631775 2014 1 None None None
Literature, cohort, and gnomAD – 6 6 0 –
Variant features alone – 15 9 1 –

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 V165M.
Neighbour residue Distance (Å) Observed variants
165 0 V165M,
164 4
162 5 V162M,
168 6 G168R, G168R, G168R, G168R,
166 6 F166V,
169 6 T169M, T169R,
163 7
161 7
167 7
206 9 V206L,
170 10
160 10 E160del, E160K, E160V,
210 10 M210I, M210I, M210I,
209 10 S209P,
158 11
172 11 V172M, V172E,
213 11
159 11 M159del,
171 11
207 12 V207M, V207L, V207L, V207L, V207L, V207del
205 12 V205M,
237 12
214 12 C214Y,
173 13
157 13 F157C,
203 13 L203P,
208 13 A208V,
202 13 D202N, D202H,
132 13 I132L,
129 13 V129I,
211 14
174 14 R174H, R174C, R174L,
212 14
156 14
233 14 L233P,
125 15
240 15 H240R, H240P,
136 15
133 15 V133I,
230 15
176 15