KCNH2 Variant M60T

Summary of observed carriers, functional annotations, and structural context for KCNH2 M60T. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

27%

3/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

M60T has not been reported in gnomAD. This residue resides in a Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 0% of WT with a standard error of 10%. 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 (%)
-4.233 0.011 -1 0.704 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 LQT2 Other Disease
Japan Cohort 2020 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
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 M60T.
Neighbour residue Distance (Å) Observed variants
60 0 M60T,
59 5
41 5 V41A,
61 5 Q61R,
57 6 A57P,
56 6 R56Q,
42 6 I42N,
44 6 C44F, C44X, C44W,
859 7 T859M, T859R,
860 7
62 7 R62Q,
797 8 A797T,
40 8
796 8 V796L, V796L, V796Del,
58 8 E58K, E58D, E58D,
43 8 Y43D, Y43C,
55 8 S55L,
798 9 I798fsX,
799 9 L799sp,
31 9 I31S,
30 10 I30Del, I30T,
63 10 P63H,
32 10 A32T,
789 10
858 11 I858V, I858T,
861 11 N861H, N861I,
803 11 D803Y, D803X,
48 11
49 11 C49R, C49G,
64 11 C64R, C64Y,
54 11 Y54N, Y54X,
45 11 N45D, N45K, N45K,
857 12 E857X,
795 12 V795I,
68 12 F68L, F68V, F68L, F68L,
66 12 C66R, C66G, C66Y,
800 12
39 12 C39R, C39X,
804 12
33 12 N33T
788 12 E788K, E788D, E788D,
862 13 L862P,
29 13 F29L, F29V, F29S, F29L, F29L,
805 13 F805S, F805C,
787 13
52 13 C52W,
46 13 D46Y, D46E, D46E,
36 13 V36X,
806 13 G806R, G806R,
38 13
53 13 G53S, G53R,
791 13 R791W, R791Q,
819 14 N819K, N819K,
127 14
65 14 T65P,
790 14
794 14 V794I, V794D,
69 14 L69Del, L69P,
47 14 G47C, G47V,
124 14 M124T, M124R,
125 15
802 15
67 15
786 15
15 15 L15V,
782 15 I782fsX, I782N,
19 15 I19F,
820 15 G820R, G820R,