Submissions for variant NM_000834.5(GRIN2B):c.2453T>C (p.Met818Thr)

dbSNP: rs879254016

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001705310	SCV000293189	pathogenic	not provided	2021-03-15	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect (Platzer et al., 2017); Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28377535)
Institute of Human Genetics, University of Leipzig Medical Center	RCV001172331	SCV001335357	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	RCV002518437	SCV003461843	pathogenic	Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27	2022-05-06	criteria provided, single submitter	clinical testing	This variant disrupts the p.Met818 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. 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: 245960). 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 818 of the GRIN2B protein (p.Met818Thr).