ClinVar Miner

Submissions for variant NM_000834.5(GRIN2B):c.448A>G (p.Ile150Val)

dbSNP: rs796052570
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001172347 SCV001335393 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 RCV001852459 SCV002181914 uncertain significance Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 2021-07-30 criteria provided, single submitter clinical testing 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 not expected to disrupt GRIN2B protein function. ClinVar contains an entry for this variant (Variation ID: 205709). This missense change has been observed in individual(s) with clinical features of GRIN2B-related conditions (PMID: 26633542, 28377535). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 150 of the GRIN2B protein (p.Ile150Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine.
Genetics and Molecular Pathology, SA Pathology RCV001172347 SCV004175269 likely pathogenic Intellectual disability, autosomal dominant 6 2023-06-29 criteria provided, single submitter clinical testing The GRIN2B c.448A>G variant is classified as LIKELY PATHOGENIC (PS4_Supporting, PS2, PM2) The GRIN2B c.448A>G variant is a single nucleotide change in exon 4/14 of the GRIN2B gene, which is predicted to change the amino acid isoleucine at position 150 in the protein to valine. This variant has been identified as a de novo variant in this patient as well as in one reported case (PMID:28377535) (PS2), and has also been reported in other individuals with intellectual disability (PMID:26633542) (PS4_supporting). This variant is absent from population databases (PM2). The variant has been reported in dbSNP (rs796052570) and in the HGMD database: CM1618931. It has been reported as likely pathogenic by other diagnostic laboratories (ClinVar Variation ID: 205709).

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