KCNH2 Variant V41L

Summary of observed carriers, functional annotations, and structural context for KCNH2 V41L. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

20%

90% CI: 4.2% – 43.1%

2/10 effective observations

Total carriers

0

0 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

V41L has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 51% of WT with a standard error of 13%. 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 2 individuals with LQT2 and 8 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-0.746 0.0 1 0.596 49

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 – 0 0 0 –
Variant features alone – 10 8 2 –

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 V41L.
Neighbour residue Distance (Å) Observed variants
41 0 V41A,
40 4
42 5 I42N,
60 5 M60T,
32 6 A32T,
59 6
31 6 I31S,
30 7 I30Del, I30T,
61 7 Q61R,
64 7 C64R, C64Y,
63 7 P63H,
62 7 R62Q,
39 7 C39R, C39X,
44 8 C44F, C44X, C44W,
796 8 V796L, V796L, V796Del,
43 8 Y43D, Y43C,
33 8 N33T
797 8 A797T,
798 9 I798fsX,
66 9 C66R, C66G, C66Y,
56 10 R56Q,
127 10
125 10
36 10 V36X,
795 10 V795I,
65 10 T65P,
57 10 A57P,
38 10
124 10 M124T, M124R,
48 11
860 11
29 11 F29L, F29V, F29S, F29L, F29L,
34 11 A34T,
126 11
58 11 E58K, E58D, E58D,
68 11 F68L, F68V, F68L, F68L,
859 11 T859M, T859R,
45 12 N45D, N45K, N45K,
789 12
55 12 S55L,
799 12 L799sp,
794 12 V794I, V794D,
35 13 R35W,
788 13 E788K, E788D, E788D,
67 13
49 13 C49R, C49G,
37 13
15 13 L15V,
54 13 Y54N, Y54X,
69 13 L69Del, L69P,
86 13 L86R,
129 13 F129C,
791 13 R791W, R791Q,
123 14
52 14 C52W,
19 14 I19F,
790 14
800 14
128 14 N128S,
112 14 V112M,
803 15 D803Y, D803X,
47 15 G47C, G47V,
861 15 N861H, N861I,
82 15 I82Del, I82dup, I82Ins, I82T,
46 15 D46Y, D46E, D46E,
28 15 K28E,