KCNH2 Variant G626V

Summary of observed carriers, functional annotations, and structural context for KCNH2 G626V. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

48%

6/14 effective observations

Total carriers

4

3 LQT2 · 1 unaffected

Functional studies

0

Publications with functional data

G626V 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 0%. 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 3 individuals with LQT2 and 7 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-8.701 0.999 -3 0.939 91

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
10862104 2000 4 1 3
Literature, cohort, and gnomAD 4 1 3
Variant features alone 10 7 3

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 G626V.
Neighbour residue Distance (Å) Observed variants
626 0 G626S, G626A, G626V,
625 4 V625E,
627 4 F627L, F627fsX, F627X, F627L, F627L,
626 5 G626S, G626A, G626V,
626 5 G626S, G626A, G626V,
620 5 S620G, S620I,
625 5 V625E,
627 5 F627L, F627fsX, F627X, F627L, F627L,
628 6 G628S, G628R, G628Del, G628D, G628A, G628V,
624 7 S624R, S624N, S624R, S624R,
621 7 S621R, S621N, S621R, S621R,
626 7 G626S, G626A, G626V,
625 7 V625E,
624 8 S624R, S624N, S624R, S624R,
625 8 V625E,
617 8 F617L, F617V, F617L, F617L,
628 8 G628S, G628R, G628Del, G628D, G628A, G628V,
623 8 T623I,
630 8 V630I, V630T, V630A,
628 8 G628S, G628R, G628Del, G628D, G628A, G628V,
624 9 S624R, S624N, S624R, S624R,
616 9 Y616S,
627 9 F627L, F627fsX, F627X, F627L, F627L,
629 9 N629D, N629T, N629S, N629I, N629K, N629K,
621 9 S621R, S621N, S621R, S621R,
620 9 S620G, S620I,
620 9 S620G, S620I,
631 9 S631F,
645 9 M645L, M645V, M645L, M645R, M645I, M645I, M645I,
627 9 F627L, F627fsX, F627X, F627L, F627L,
624 9 S624R, S624N, S624R, S624R,
631 10 S631F,
628 10 G628S, G628R, G628Del, G628D, G628A, G628V,
622 10 L622F,
629 10 N629D, N629T, N629S, N629I, N629K, N629K,
641 10 S641P, S641F,
632 10 P632A, P632S,
618 11 T618S, T618S,
645 11 M645L, M645V, M645L, M645R, M645I, M645I, M645I,
623 11 T623I,
619 11
632 11 P632A, P632S,
641 11 S641P, S641F,
630 11 V630I, V630T, V630A,
623 11 T623I,
617 11 F617L, F617V, F617L, F617L,
621 11 S621R, S621N, S621R, S621R,
616 12 Y616S,
629 12 N629D, N629T, N629S, N629I, N629K, N629K,
620 12 S620G, S620I,
630 12 V630I, V630T, V630A,
644 12 V644I, V644F,
642 12 I642V, I642Del,
638 12 K638E, K638D, K638Del, K638R,
622 12 L622F,
621 13 S621R, S621N, S621R, S621R,
644 13 V644I, V644F,
613 13 T613A, T613L, T613K, T613M,
617 13 F617L, F617V, F617L, F617L,
623 13 T623I,
631 13 S631F,
629 13 N629D, N629T, N629S, N629I, N629K, N629K,
614 13 A614T, A614V,
616 13 Y616S,
615 13 L615V, L615F,
648 13 G648A,
618 14 T618S, T618S,
631 14 S631F,
645 14 M645L, M645V, M645L, M645R, M645I, M645I, M645I,
652 14 Y652X
633 14 N633D, N633S, N633I,
568 14 W568C, W568C,
648 14 G648A,
622 14 L622F,
642 14 I642V, I642Del,
630 14 V630I, V630T, V630A,
619 14
649 14
638 14 K638E, K638D, K638Del, K638R,
640 14 F640L, F640V, F640Del, F640L, F640L,
633 15 N633D, N633S, N633I,
645 15 M645L, M645V, M645L, M645R, M645I, M645I, M645I,
649 15
619 15
640 15 F640L, F640V, F640Del, F640L, F640L,
585 15 W585C, W585C,
646 15
637 15 E637K, E637G, E637X,
632 15 P632A, P632S,
637 15 E637K, E637G, E637X,
618 15 T618S, T618S,
652 15 Y652X