KCNQ1 Variant A178S

Summary of observed carriers, functional annotations, and structural context for KCNQ1 A178S. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT1 penetrance

72%

7/10 effective observations

Total carriers

0

0 LQT1 · 0 unaffected

Functional studies

0

Publications with functional data

A178S has not been reported in gnomAD. This residue resides in a Hotspot region for LQT1.

Variant features alone are equivalent to phenotyping 7 individuals with LQT1 and 3 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT1 (%)
-1.93 0.994 1 0.709 78

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 – 0 0 0 –
Variant features alone – 15 3 7 –

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 A178S.
Neighbour residue Distance (Å) Observed variants
178 0 A178T, A178del,
179 4 G179S,
177 4 S177F,
180 5
184 5 Y184S, Y184C, Y184D, Y184H
190 5 R190W, R190Q, R190L,
111 6 Y111C,
181 6 R181C,
193 6 F193L, F193L, F193L,
175 7 L175I,
189 7 G189R, G189R, G189E,
185 8 V185L, V185L, V185M, V185del,
107 8 Q107H, Q107H,
186 8 G186R, G186D,
176 8
108 9 G108S,
183 9 K183R,
182 9
174 9 R174H, R174C, R174L,
115 9 E115A, E115G,
110 9 V110I,
173 9
114 10
194 10 A194P, A194T,
112 10
188 11 W188C, W188C, W188G, W188S,
172 11 V172M, V172E,
191 11
192 11 R192C, R192H,
187 11 L187P, L187F,
171 11
116 11
196 12
106 12
199 12 S199A,
244 13
104 13 T104A, T104I,
170 13
105 13
113 13
109 13 R109C, R109L,
195 13 R195Q, R195W,
243 14 R243H, R243C, R243P, R243S,
198 14 I198V, I198T,
117 15 P117L,
202 15 D202N, D202H,