KCNH2 Variant V131L

Summary of observed carriers, functional annotations, and structural context for KCNH2 V131L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

3%

0/31 effective observations

Total carriers

21

0 LQT2 · 5 unaffected

Functional studies

0

Publications with functional data

V131L is present in 21 alleles in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 113% of WT with a standard error of 18%. 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 0 individuals with LQT2 and 10 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-0.286 0.0 1 0.364 21

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 – 21 5 0 –
Variant features alone – 10 10 0 –

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 V131L.
Neighbour residue Distance (Å) Observed variants
131 0 V131L, V131L, V131fsX,
130 4 E130K,
108 5 C108Y,
107 6 L107P,
109 7 L109X, L109Q, L109P,
106 8 F106L, F106V, F106L, F106L,
129 9 F129C,
28 9 K28E,
51 9
95 10 E95K, E95G,
110 11 V110A,
128 11 N128S,
97 11
98 11
96 11 I96V, I96T,
105 11
27 12 R27X, R27P,
100 12 R100G, R100Q, R100P,
111 12 D111V,
47 12 G47C, G47V,
93 12 K93X, K93R,
26 13 S26I,
48 13
94 13 V94L, V94L, V94A,
50 13 E50X,
52 13 C52W,
104 14
99 14 Y99N, Y99S,
127 14
29 15 F29L, F29V, F29S, F29L, F29L
69 15 L69Del, L69P,
25 15 Q25P,