KCNH2 Variant A671Del

Summary of observed carriers, functional annotations, and structural context for KCNH2 A671Del. Data combine curated literature, international cohorts, and gnomAD observations.

Estimated LQT2 penetrance

26%

90% CI: 7.8% – 49.0%

2/11 effective observations

Total carriers

1

1 LQT2 · 0 unaffected

Functional studies

0

Publications with functional data

A671Del has not been reported in gnomAD. This residue resides in a Mild_Hotspot region for LQT2.

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 (%)
None None None None 33

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
15840476 2005 1 0 1
Literature, cohort, and gnomAD – 1 0 1 –
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 A671Del.
Neighbour residue Distance (Å) Observed variants
671 0 A671G, A671Del,
670 4
669 5 G669R, G669C, G669X,
672 5 R672C, R672H,
668 5 S668L,
674 6 H674Y, H674fsX,
675 6
673 7
664 7 Q664X,
667 8 Y667X,
665 9 R665Q,
676 9 Q676fsX, Q676X,
705 10 W705fsX, W705X,
710 10
658 10
661 10 A661V,
666 10
677 11 M677T,
663 11
662 11
678 11
543 11 S543fsX,
665 12 R665Q,
661 12 A661V,
709 12
679 12 R679W, R679Q,
657 13 G657S, G657V,
549 13 V549M,
701 13
662 13
711 13 I711V,
660 13 S660L,
546 13
664 13 Q664X,
540 13 D540fsX,
539 14
654 14
659 14
660 14 S660L,
668 14 S668L,
702 14
675 14
682 14 E682X,
544 14 E544A, E544fsX,
706 14 S706C, S706F,
681 14 R681W,
708 14
679 15 R679W, R679Q,
678 15
666 15
680 15
712 15 D712N
553 15 L553V,