ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.345_347GAA[1] (p.Lys116del) (rs864622157)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205717 SCV000259493 uncertain significance Long QT syndrome 2015-07-18 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 3 of the KCNH2 mRNA (c.348_350delGAA). This leads to the deletion of 1 amino acid residue in the KCNH2 protein (p.Lys116del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases and has not been published in the literature. The lysine at codon position 116 falls in a region of the KCNH2 protein whose function is not understood. In summary this is a novel in-frame deletion of 1 amino acid in exon 3 of the KCNH2 protein, affecting a region of the protein which is not predicted to be involved with a functional domain. For these reasons, this sequence change has been classified as a Variant of Uncertain Significance.
GeneDx RCV000599424 SCV000710009 uncertain significance not specified 2017-11-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNH2 gene. The c.348_350delGAA variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed in large population cohorts (Lek et al., 2016). The c.348_350delGAA variant results in an in-frame deletion of a lysine residue, denoted p.K116del at a position that is conserved across species. Additionally, this variant is located in the PAS-associated C-terminal (PAC) domain, which, although distinct from the pore region, has been suggested to be enriched for pathogenic variants (Kapa et al., 2009). Furthermore, other in-frame deletions have been reported in the Human Genome Mutation database in association with LQTS (Stenson et al., 2014). However, this variant lacks observation in a significant number of affected individuals, segregation data, and functional evidence, which would further clarify its pathogenicity.

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