ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1987G>T (p.Asp663Tyr) (rs794728402)

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
GeneDx RCV000181906 SCV000234209 likely pathogenic not provided 2014-07-16 criteria provided, single submitter clinical testing p.Asp1003Tyr (GAC>TAC): c.3007 G>T in exon 13 of the KCNH2 gene (NM_000238.2). The D1003Y variant that is likely pathogenic was identified in the KCNH2 gene. The D1003Y variant in the KCNH2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The D1003Y variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The D1003Y residue is class conserved across species. In silico analysis predicts D1003Y is damaging to the protein structure/function. Mutations in nearby residues (N996I, R1005Q, R1007H) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. Furthermore, the D1003Y variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in LQT panel(s).

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.