ClinVar Miner

Submissions for variant NM_020433.5(JPH2):c.1729G>A (p.Glu577Lys)

gnomAD frequency: 0.00001  dbSNP: rs181096982
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 RCV000183464 SCV000235924 likely benign not specified 2014-10-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001327461 SCV001518538 uncertain significance Hypertrophic cardiomyopathy 2022-09-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 577 of the JPH2 protein (p.Glu577Lys). This variant is present in population databases (rs181096982, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. ClinVar contains an entry for this variant (Variation ID: 201793). This variant has not been reported in the literature in individuals affected with JPH2-related conditions.
Ambry Genetics RCV002399669 SCV002713727 uncertain significance Cardiovascular phenotype 2021-09-30 criteria provided, single submitter clinical testing The p.E577K variant (also known as c.1729G>A), located in coding exon 4 of the JPH2 gene, results from a G to A substitution at nucleotide position 1729. The glutamic acid at codon 577 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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.