ClinVar Miner

Submissions for variant NM_000834.5(GRIN2B):c.1672G>A (p.Val558Ile)

dbSNP: rs1057519004
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000988791 SCV001138653 pathogenic Intellectual disability, autosomal dominant 6 2019-05-28 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000988791 SCV001335416 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).
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV002252116 SCV002522908 likely pathogenic See cases 2021-11-23 criteria provided, single submitter clinical testing ACMG classification criteria: PS4, PM2, PM6, PP2, BP4
GeneDx RCV003324745 SCV004030621 pathogenic not provided 2023-08-24 criteria provided, single submitter clinical testing Published functional studies demonstrate that V558I affected some GluN2B containing NMDAR channel property (Vyklivky et al., 2018); Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28867141, 29681796, 28377535, 27839871)
Invitae RCV003766167 SCV004570857 pathogenic Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 2023-01-26 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GRIN2B function (PMID: 28377535, 29681796). 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. ClinVar contains an entry for this variant (Variation ID: 374243). This missense change has been observed in individual(s) with autosomal dominant intellectual disability (PMID: 28377535). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 558 of the GRIN2B protein (p.Val558Ile).
Laboratory of Molecular Genetics, CHU Rennes RCV000414971 SCV000493101 likely pathogenic intellectual deficiency no assertion criteria provided clinical testing
Genetic Services Laboratory, University of Chicago RCV000500367 SCV000595084 uncertain significance not specified 2016-05-05 flagged submission clinical testing
GenomeConnect - Simons Searchlight RCV001265247 SCV001443361 likely pathogenic Complex neurodevelopmental disorder 2015-12-23 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2015-12-23 and interpreted as Likely Pathogenic. Variant was initially reported on 2015-10-08 by GTR ID of laboratory name 279559. The reporting laboratory might also submit to ClinVar.

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