ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1693G>C (p.Ala565Pro) (rs199473518)

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 RCV000181810 SCV000234113 likely pathogenic not provided 2015-02-02 criteria provided, single submitter clinical testing p.Ala565Pro (GCC>CCC): c.1693 G>C in exon 7 of the KCNH2 (HERG) gene (NM_000238.2). A missense variant that is likely pathogenic was identified in the KCNH2 gene. The A565P variant in has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The A565P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts A565P is probably damaging to the protein structure/function. A mutations at this residue (A565T) and in nearby residues (W563G, W563C, L564P, C566G, C566S, C566F, I567T ) have been reported in association with LQTS (Kapplinger J et al., 2009), further supporting the functional importance of this residue and this region of the protein. Furthermore, A565P 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.