Submissions for variant NM_000834.5(GRIN2B):c.2252T>C (p.Ile751Thr)

dbSNP: rs876661055

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000217622	SCV000279381	pathogenic	not provided	2023-03-24	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32144935, 28377535, 27848944, 31526516, 35893069, 36758276, 27839871)
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625193	SCV000744079	pathogenic	Intellectual disability, autosomal dominant 6	2017-07-28	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625193	SCV000745553	likely pathogenic	Intellectual disability, autosomal dominant 6	2017-05-31	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000625193	SCV001335352	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).
Diagnostic Laboratory, Strasbourg University Hospital	RCV001260713	SCV001437805	pathogenic	Intellectual disability	2020-09-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002519747	SCV003441200	pathogenic	Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27	2022-07-09	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 751 of the GRIN2B protein (p.Ile751Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with intellectual disability (PMID: 28377535). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 234500). 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. For these reasons, this variant has been classified as Pathogenic.
GenomeConnect - Simons Searchlight	RCV001265388	SCV001443513	pathogenic	Complex neurodevelopmental disorder	2019-02-01	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2019-02-01 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000217622	SCV001741638	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000217622	SCV001954761	pathogenic	not provided		no assertion criteria provided	clinical testing
Molecular Genetics laboratory, Necker Hospital	RCV000217622	SCV004031312	pathogenic	not provided	2023-03-29	no assertion criteria provided	clinical testing