ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.2180_2317del (p.Asp727_Ala772del) (rs1554425226)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000530429 SCV000627451 likely pathogenic Long QT syndrome 2017-02-07 criteria provided, single submitter clinical testing This sequence change deletes 138 nucleotides from exon 9 of the KCNH2 mRNA (c.2180_2317del). This leads to the deletion of 46 amino acid residues in the KCNH2 protein (p.Asp727_Ala772del) but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a KCNH2-related disease. Experimental studies have shown that several missense changes (p.Ser735Leu, p.Gly749Val, p.Arg752Gln, p.Lys757Asn, and p.Val770Ala) in this region of the KCNH2 gene have a deleterious effect on protein trafficking (PMID: 25417810). This variant identified in the KCNH2 gene is located in the cytoplasmic C-terminal region of the resulting protein and deletes part of the cytoplasmic cyclic nucleotide binding region (PMID: 19841300, 25348405). For more information about the location of this variant, please visit Missense substitutions at residues deleted by this variant (such as p.Arg752Trp) have been determined to be pathogenic (PMID: 11009462, 11854117). This suggests that there are residues in this region that are critical for KCNH2 protein function and and the loss of these residues may also be pathogenic. In summary, this variant is a novel in-frame deletion that affects residues that are important for normal protein function. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.