KCNH2 Variant S179W

Summary of observed carriers, functional annotations, and structural context for KCNH2 S179W. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

12%

1/11 effective observations

Total carriers

1

0 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

S179W is present in 1 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 20%. In our analysis we used SE < 20% as 'high quality'. Approximately below 50% of WT is considered PS3 moderate and below 30% is PS3 strong.

Variant features alone are equivalent to phenotyping 1 individuals with LQT2 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-2.989 1.0 -4 0.587 14

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 LQT2 Other Disease
Literature, cohort, and gnomAD – 1 1 0 –
Variant features alone – 10 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. Note that some residues appear multiple times at different distances since the functional KV11.1 channel (protein product of KCNH2/hERG) is a homotetramer and occasionally the same residue from multiple subunits is present within the 15Å window.

Previously observed variants near S179W.
Neighbour residue Distance (Å) Observed variants
179 0 S179W,
178 4
180 4
177 5 E177X,
181 5 R181Q, R181fsX, R181W,
176 7 R176X, R176Q, R176W,
182 7 S182X,
175 8 A175S, A175X, A175D,
183 8 G183fsX,
174 8
184 8 G184Del,
173 9
185 9
172 10 A172V,
186 10 G186fsX,
171 11 L171Ins,
187 11 G187X, G187S, G187A, G187Del,
170 11 L170Ins,
188 11 A188S, A188P, A188X,
169 12 A169G,
189 12 G189Ins,
168 13
190 13 A190T, A190V,
167 13
191 13 P191Q, P191fsX,
166 14
192 14 G192fsX,
165 14
193 14 A193fsX, A193V, A193X, A193T,
164 15 R164C, R164H
194 15 V194M,