KCNH2 Variant G572C

Summary of observed carriers, functional annotations, and structural context for KCNH2 G572C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

50%

90% CI: 32.1% – 74.5%

7/14 effective observations

Total carriers

4

4 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

G572C 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 4%. 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 (%)
-8.434 1.0 -3 0.976 88

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
14642687 2003 1 0 1
9693036 1998 2 0 2
Literature, cohort, and gnomAD – 4 0 4 –
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 G572C.
Neighbour residue Distance (Å) Observed variants
572 0 G572S, G572R, G572C, G572D,
573 4
571 4 I571L, I571V,
570 5
575 6 E575K,
569 6 Y569H, Y569C, Y569X,
586 6 L586M,
576 6
585 6 W585C, W585C,
574 6 M574L, M574V, M574L,
568 7 W568C, W568C,
584 8 G584S, G584R, G584C,
637 8 E637K, E637G, E637X,
636 9
587 9
634 9 T634P, T634A, T634S, T634S, T634I,
577 10
567 10 I567T, I567M,
610 10
583 10 I583V,
430 11
431 11 F431L, F431L, F431L,
566 11 C566S, C566R, C566G, C566S, C566F,
614 11 A614T, A614V,
565 11
640 11 F640L, F640V, F640Del, F640L, F640L,
589 12 L589P,
633 12 N633D, N633S, N633I,
588 12 N588D, N588K, N588K,
597 12 Y597H, Y597C,
632 12 P632A, P632S,
613 12 T613A, T613L, T613K, T613M,
635 12 N635I,
605 12 P605L,
631 13 S631F,
617 13 F617L, F617V, F617L, F617L,
630 13 V630I, V630T, V630A,
638 13 K638E, K638D, K638Del, K638R,
590 13 G590D, G590V,
607 14
639 14 I639F, I639N,
564 14 L564L,
609 14 D609N, D609G,
604 14 G604S, G604C, G604D,
429 14 A429P, A429V,
611 14 Y611D,
432 14
641 14 S641P, S641F
606 15 S606Del, S606P, S606F,
618 15 T618S, T618S,
603 15 G603D,