KCNQ1 Variant S199A

Summary of observed carriers, functional annotations, and structural context for KCNQ1 S199A. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

69%

7/11 effective observations

Total carriers

1

1 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

S199A has not been reported in gnomAD. This residue resides in a Hotspot 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 (%)
-1.32 0.197 -1 0.799 69

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
19716085 2009 1 None 1 None
Literature, cohort, and gnomAD – 1 0 1 –
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 S199A.
Neighbour residue Distance (Å) Observed variants
199 0 S199A,
200 4
198 4 I198V, I198T,
202 5 D202N, D202H,
194 5 A194P, A194T,
196 5
197 6 P197L,
201 6 I201del,
171 7
203 7 L203P,
193 7 F193L, F193L, F193L,
174 8 R174H, R174C, R174L,
204 9 I204M, I204F,
243 9 R243H, R243C, R243P, R243S,
240 9 H240R, H240P,
175 9 L175I,
195 9 R195Q, R195W,
115 10 E115A, E115G,
205 10 V205M,
244 10
206 10 V206L,
191 11
170 11
239 11
172 11 V172M, V172E,
168 11 G168R, G168R, G168R, G168R,
184 12 Y184S, Y184C, Y184D, Y184H
245 12 G245V,
242 12 D242N, D242Y,
190 12 R190W, R190Q, R190L,
178 12 A178T, A178del,
167 12
114 12
236 12 L236Q, L236R,
207 12 V207M, V207L, V207L, V207L, V207L, V207del,
189 12 G189R, G189R, G189E,
192 12 R192C, R192H,
111 13 Y111C,
173 13
248 13 W248C, W248C, W248R, W248R,
177 13 S177F,
241 13 V241F, V241I, V241G,
237 13
183 14 K183R,
169 14 T169M, T169R,
181 14 R181C,
208 14 A208V,
176 14
233 15 L233P,
246 15
164 15
187 15 L187P, L187F,