Submissions for variant NM_000834.5(GRIN2B):c.2116A>G (p.Met706Val)

dbSNP: rs1057518988

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, University of Leipzig Medical Center	RCV001172325	SCV001335350	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	RCV001376742	SCV001573903	likely pathogenic	Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27	2020-04-01	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with clinical features of GRIN2B-related conditions (PMID: 28377535, 28333917, 27818011, 28867141). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 374226). This variant has been reported not to substantially affect GRIN2B protein function (PMID: 28377535). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces methionine with valine at codon 706 of the GRIN2B protein (p.Met706Val). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and valine. This variant is not present in population databases (ExAC no frequency).
GeneDx	RCV001723972	SCV005326261	pathogenic	not provided	2024-02-02	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: 35240744, 27818011, 28867141, 36645496, 27839871, 28333917, 28377535, 27479843)
Laboratory of Molecular Genetics, CHU Rennes	RCV000414945	SCV000493078	likely pathogenic	Epilepsy; Dyssynergia; intellectual deficiency		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001723972	SCV001955441	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001723972	SCV001964221	pathogenic	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001723972	SCV002036062	likely pathogenic	not provided		no assertion criteria provided	clinical testing