KCNH2 Variant R672C

Summary of observed carriers, functional annotations, and structural context for KCNH2 R672C. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

8%

1/14 effective observations

Total carriers

4

0 LQT2 · 2 unaffected

Functional studies

0

Publications with functional data

R672C is present in 4 alleles in gnomAD. This residue resides in a Non_Hotspot region for LQT2.

We have tested the trafficking efficiency of this variant: 87% of WT with a standard error of 17%. 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 (%)
-7.751 1.0 -4 0.873 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 – 4 2 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 R672C.
Neighbour residue Distance (Å) Observed variants
672 0 R672C, R672H,
669 4 G669R, G669C, G669X,
671 5 A671G, A671Del,
668 5 S668L,
710 6
670 6
673 7
675 7
676 7 Q676fsX, Q676X,
705 7 W705fsX, W705X,
674 8 H674Y, H674fsX,
711 9 I711V,
709 9
712 10 D712N,
664 10 Q664X,
708 10
679 11 R679W, R679Q,
677 11 M677T,
667 11 Y667X,
701 11
682 11 E682X,
679 11 R679W, R679Q,
666 12
665 12 R665Q,
706 12 S706C, S706F,
675 12
678 12
665 12 R665Q,
678 12
704 12 A704T, A704V,
702 13
713 14 M713V,
663 14
661 14 A661V,
680 14
676 14 Q676fsX, Q676X,
661 14 A661V,
719 15
715 15 A715T, A715A, A715V, A715sp
707 15
662 15
658 15
543 15 S543fsX,