ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.26C>T (p.Ala9Val) (rs775317201)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181953 SCV000234256 uncertain significance not provided 2019-01-07 criteria provided, single submitter clinical testing The Ala9Val variant in the KCNH2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Ala9Val results in a conservative amino acid substitution of one non-polar amino acid with another at a position that is conserved across species. In silico analysis predicts Ala9Val is probably damaging to the protein structure/function. Mutations in nearby codons (Met1Leu, Asp16Ala) have been reported in association with LQTS, supporting the functional importance of this region of the protein. The NHLBI ESP Exome Variant Server reports Ala9Val was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations.With the clinical and molecular information available at this time, we cannot definitively determine if Ala9Val is a disease-causing mutation or a rare benign variant.
Invitae RCV000469823 SCV000543446 uncertain significance Long QT syndrome 2016-07-18 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 9 of the KCNH2 protein (p.Ala9Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. The frequency data for this variant (rs775317201) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a KCNH2-related disease. ClinVar contains an entry for this variant (Variation ID: 200592). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000181953 SCV000924812 uncertain significance not provided 2016-09-12 no assertion criteria provided provider interpretation

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.