KCNQ1 Variant M238V

Summary of observed carriers, functional annotations, and structural context for KCNQ1 M238V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

18%

2/12 effective observations

Total carriers

2

0 LQT1 · 2 unaffected

Functional studies

0

Publications with functional data

M238V is present in 2 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 (%)
-3.89 0.798 4 0.903 19

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 – 2 2 0 –
Variant features alone – 15 8 2 –

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 M238V.
Neighbour residue Distance (Å) Observed variants
238 0 M238V, M238L, M238L,
239 5
235 6 I235N,
271 6
130 6
133 6 V133I,
134 7 L134P,
241 7 V241F, V241I, V241G,
137 7 L137F, L137P,
236 7 L236Q, L236R,
267 7 Y267C
240 7 H240R, H240P,
237 8
274 8 I274V,
234 8 Q234H, Q234H,
275 8 F275del,
242 9 D242N, D242Y,
136 10
270 10 F270S,
272 10 G272D, G272S, G272V,
268 10 I268V, I268S,
129 11 V129I,
233 11 L233P,
131 11
232 11
248 11 W248C, W248C, W248R, W248R,
132 11 I132L,
269 11 G269D, G269S, G269del,
135 11
273 11 L273F, L273V, L273R,
138 12
201 12 I201del,
243 12 R243H, R243C, R243P, R243S,
205 12 V205M,
247 12 T247I,
140 12 S140G, S140R, S140R, S140R,
202 12 D202N, D202H,
278 12 Y278H,
198 12 I198V, I198T,
127 13 F127L, F127L, F127L,
167 13
128 13 A128del,
126 13 H126D,
277 13 S277L, S277del, S277P, S277W,
299 13
266 13 L266P,
303 13 L303P,
276 13 S276del,
231 14 R231C, R231H, R231S,
141 14 V141M,
245 14 G245V,
230 14
264 14
163 14
139 14
229 14 G229D,
246 14
160 14 E160del, E160K, E160V,
263 15
279 15 F279I,
265 15 T265I,
204 15 I204M, I204F,