ClinVar Miner

Submissions for variant NM_000834.5(GRIN2B):c.2459G>C (p.Gly820Ala)

dbSNP: rs797044849
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000190648 SCV000244088 pathogenic Inborn genetic diseases 2019-01-18 criteria provided, single submitter clinical testing
GeneDx RCV000235569 SCV000293376 pathogenic not provided 2021-04-01 criteria provided, single submitter clinical testing Published functional studies demonstrate that G820A stabilizes long-lived open states leading to slow deactivation and high Ca2+ permeability (Amin et al., 2018); This variant is associated with the following publications: (PMID: 28867141, 27818011, 28135719, 28856709, 28377535, 29681796, 30217972, 28191890, 33490948, 32144935, 33176815)
Invitae RCV000464558 SCV000552119 pathogenic Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 2023-03-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly820 amino acid residue in GRIN2B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25356899). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 208643). This missense change has been observed in individual(s) with clinical features of epileptic encephalopathy and developmental delay (PMID: 28856709; Invitae). In at least one individual the variant was observed to be de novo. This variant is present in population databases (rs797044849, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 820 of the GRIN2B protein (p.Gly820Ala).
Undiagnosed Diseases Network, NIH RCV000791283 SCV000930581 likely pathogenic Intellectual disability, autosomal dominant 6 2019-02-08 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000791283 SCV001335375 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).
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000791283 SCV001976966 pathogenic Intellectual disability, autosomal dominant 6 2021-10-01 criteria provided, single submitter clinical testing PS2, PM1, PM2, PM5, PP2, PP3
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000791283 SCV003932141 pathogenic Intellectual disability, autosomal dominant 6 2023-02-21 criteria provided, single submitter clinical testing PS3_Moderate, PM2, PM6_Strong, PP2, PP3
GenomeConnect - Simons Searchlight RCV001265246 SCV001443360 pathogenic Complex neurodevelopmental disorder 2018-10-22 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-10-22 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000235569 SCV001931004 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000235569 SCV001959693 pathogenic not provided no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000235569 SCV001963223 pathogenic not provided no assertion criteria provided clinical testing

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