Submissions for variant NM_000834.5(GRIN2B):c.1555C>T (p.Arg519Ter)

gnomAD frequency: 0.00001  dbSNP: rs774592932

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000426345	SCV000534895	pathogenic	not provided	2022-12-09	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27824329, 31981491, 33043365, 33004838)
Diagnostic Laboratory, Strasbourg University Hospital	RCV001260712	SCV001437804	pathogenic	Intellectual disability	2020-09-10	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV001823138	SCV002073020	pathogenic	Developmental and epileptic encephalopathy, 27		criteria provided, single submitter	clinical testing	The stop gained p.R519* in GRIN2B (NM_000834.5) has been submitted to ClinVar as Pathogenic by multiple submitters but no details are available for independent assesment. It has not been reported in literature in affected individuals. It is novel (not in any individuals) in gnomAD Exomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function mutations have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001252256	SCV006072977	pathogenic	Intellectual disability, autosomal dominant 6	2025-04-21	criteria provided, single submitter	clinical testing	Variant summary: GRIN2B c.1555C>T (p.Arg519X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.1555C>T has been observed in the heterozygous state in at least one individual affected with developmental delay, seizures, and abnormal EEG (e.g. Khalaf_2024). The following publication has been ascertained in the context of this evaluation (PMID: 38438125). ClinVar contains an entry for this variant (Variation ID: 391757). Based on the evidence outlined above, the variant was classified as pathogenic.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001252256	SCV001428008	pathogenic	Intellectual disability, autosomal dominant 6	2019-01-01	no assertion criteria provided	clinical testing
GenomeConnect - Simons Searchlight	RCV001265387	SCV001443512	pathogenic	Complex neurodevelopmental disorder	2018-09-28	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-09-28 and interpreted as Pathogenic. Variant was initially reported on 2017-01-12 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000426345	SCV001808515	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000426345	SCV001956675	likely pathogenic	not provided		no assertion criteria provided	clinical testing