ClinVar Miner

Submissions for variant NM_005458.8(GABBR2):c.2360G>A (p.Arg787His)

gnomAD frequency: 0.00001  dbSNP: rs578253809
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001874631 SCV002129696 uncertain significance Epileptic encephalopathy 2021-06-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 787 of the GABBR2 protein (p.Arg787His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs578253809, ExAC 0.01%). This variant has not been reported in the literature in individuals with GABBR2-related conditions. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV003444944 SCV004171360 uncertain significance Developmental and epileptic encephalopathy, 59 criteria provided, single submitter clinical testing The missense c.2360G>A(p.Arg787His) variant in GABBR2 gene has not been reported previously as a pathogenic variant nor a benign variant, to our knowledge. The p.Arg787His variant is novel (not in any individuals) in gnomAD Exomes database. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Arg787His in GABBR2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 787 is changed to a His changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).

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.