Submissions for variant NM_000834.5(GRIN2B):c.1832G>T (p.Gly611Val)

dbSNP: rs1555110843

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, University of Leipzig Medical Center	RCV001172363	SCV001335418	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).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001852460	SCV002143450	pathogenic	Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27	2022-09-02	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 611 of the GRIN2B protein (p.Gly611Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of GRIN2B-related conditions (PMID: 28377535). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 205730). 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. Experimental studies have shown that this missense change affects GRIN2B function (PMID: 28377535, 31429998). This variant disrupts the p.Gly611 amino acid residue in GRIN2B. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
GenomeConnect - Simons Searchlight	RCV001265249	SCV001443363	likely pathogenic	Complex neurodevelopmental disorder	2016-08-11	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2016-08-11 and interpreted as Likely Pathogenic. Variant was initially reported on 2014-12-05 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.