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

dbSNP: rs797044849

Total submissions: 11

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)
Labcorp Genetics (formerly Invitae), Labcorp	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