KCNQ1 Variant I198V

Summary of observed carriers, functional annotations, and structural context for KCNQ1 I198V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

37%

6/17 effective observations

Total carriers

7

2 LQT1 · 5 unaffected

Functional studies

0

Publications with functional data

I198V is present in 5 alleles in gnomAD. This residue resides in a Hotspot region for LQT1.

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

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-0.92 0.778 -1 0.806 43

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
24606995 2014 1 None 1 None
22677073 2012 1 None None SUDS
Literature, cohort, and gnomAD – 7 5 2 –
Variant features alone – 15 6 4 –

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 I198V.
Neighbour residue Distance (Å) Observed variants
198 0 I198V, I198T,
199 4 S199A,
197 5 P197L,
196 5
201 5 I201del,
243 6 R243H, R243C, R243P, R243S,
202 6 D202N, D202H,
200 7
240 7 H240R, H240P,
244 7
242 7 D242N, D242Y,
245 8 G245V,
239 8
248 8 W248C, W248C, W248R, W248R,
194 9 A194P, A194T,
115 9 E115A, E115G,
193 9 F193L, F193L, F193L,
241 9 V241F, V241I, V241G,
174 10 R174H, R174C, R174L,
171 10
203 10 L203P,
204 10 I204M, I204F,
236 10 L236Q, L236R,
246 11
205 11 V205M,
249 12 R249S, R249S,
247 12 T247I,
114 12
170 12
195 12 R195Q, R195W,
237 12
175 12 L175I,
238 12 M238V, M238L, M238L,
167 13
206 13 V206L,
111 13 Y111C,
126 13 H126D,
184 13 Y184S, Y184C, Y184D, Y184H,
267 14 Y267C
168 14 G168R, G168R, G168R, G168R,
116 14
271 14
117 14 P117L,
178 14 A178T, A178del,
233 14 L233P,
130 14
235 14 I235N,
268 14 I268V, I268S,
172 15 V172M, V172E,
177 15 S177F,
129 15 V129I,
191 15
173 15
207 15 V207M, V207L, V207L, V207L, V207L, V207del,
192 15 R192C, R192H,
183 15 K183R,
181 15 R181C,