Submissions for variant NM_000834.5(GRIN2B):c.2087G>A (p.Arg696His)

dbSNP: rs1555103971

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000624241	SCV000740775	likely pathogenic	Inborn genetic diseases	2019-02-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000689699	SCV000817363	pathogenic	Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27	2024-04-23	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 696 of the GRIN2B protein (p.Arg696His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with intellectual disability, developmental delay, and autistic features (PMID: 27839871, 28377535). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 489393). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects GRIN2B function (PMID: 27839871). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000578652	SCV001150124	likely pathogenic	Intellectual disability, autosomal dominant 6	2019-05-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001092381	SCV001248868	pathogenic	not provided	2019-04-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000578652	SCV001335349	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	RCV001260643	SCV001437735	likely pathogenic	Intellectual disability	2020-09-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001092381	SCV003840725	pathogenic	not provided	2023-03-10	criteria provided, single submitter	clinical testing	Published functional studies demonstrate enhanced glutamate potency (Swanger et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28377535, 27818011, 31209962, 31144778, 28714951, 31981491, 33004838, 27839871)
GenomeConnect, ClinGen	RCV000578652	SCV000681402	not provided	Intellectual disability, autosomal dominant 6		no assertion provided	phenotyping only	Variant interpreted as "variant, likely mutation" and reported on 11/25/2014 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect - Simons Searchlight	RCV001265245	SCV001443359	likely pathogenic	Complex neurodevelopmental disorder	2018-09-05	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-09-05 and interpreted as Likely Pathogenic. Variant was initially reported on 2014-11-25 by GTR ID of laboratory name 61756. The reporting laboratory might also submit to ClinVar.