KCNH2 Variant R679W

Summary of observed carriers, functional annotations, and structural context for KCNH2 R679W. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

7%

1/18 effective observations

Total carriers

8

0 LQT2 · 5 unaffected

Functional studies

0

Publications with functional data

R679W is present in 8 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 83% of WT with a standard error of 26%. 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 1 individuals with LQT2 and 9 unaffected individuals.

In silico predictors

Variant-level computational predictors.
PROVEAN PolyPhen-2 BLAST-PSSM REVEL Penetrance Density LQT2 (%)
-7.765 1.0 -3 0.88 6

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 – 8 5 0 –
Variant features alone – 10 9 1 –

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 R679W.
Neighbour residue Distance (Å) Observed variants
679 0 R679W, R679Q,
676 5 Q676fsX, Q676X,
675 6
678 6
680 6
716 7 V716G,
682 7 E682X,
711 7 I711V,
712 7 D712N,
715 8 A715T, A715A, A715V, A715sp,
677 8 M677T,
683 8
710 9
713 9 M713V,
681 10 R681W,
701 10
668 11 S668L,
672 11 R672C, R672H,
674 11 H674Y, H674fsX,
673 11
709 11
717 11 L717P
672 11 R672C, R672H,
719 11
684 11
665 11 R665Q,
708 11
714 12
720 12
718 12
669 12 G669R, G669C, G669X,
686 12
671 12 A671G, A671Del,
685 13 R685C, R685H, R685P,
697 13 L697X,
710 13
687 13
705 14 W705fsX, W705X,
698 14 E698K, E698X,
705 14 W705fsX, W705X,
666 14
669 14 G669R, G669C, G669X,
671 15 A671G, A671Del,
702 15
712 15 D712N,
670 15
700 15