ClinVar Miner

Submissions for variant NM_000834.5(GRIN2B):c.2453T>C (p.Met818Thr)

dbSNP: rs879254016
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 RCV001705310 SCV000293189 pathogenic not provided 2021-03-15 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (Platzer et al., 2017); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28377535)
Institute of Human Genetics, University of Leipzig Medical Center RCV001172331 SCV001335357 likely pathogenic Intellectual disability, autosomal dominant 6 2017-04-04 criteria provided, single submitter clinical testing This variant was identified as de novo (maternity and paternity confirmed).
Invitae RCV002518437 SCV003461843 pathogenic Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 2022-05-06 criteria provided, single submitter clinical testing This variant disrupts the p.Met818 amino acid residue in GRIN2B. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GRIN2B protein function. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 818 of the GRIN2B protein (p.Met818Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of GRIN2B-related conditions (PMID: 28377535). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 245960).

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.