Submissions for variant NM_000834.5(GRIN2B):c.2452A>C (p.Met818Leu)

dbSNP: rs876661076

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000214028	SCV000279463	likely pathogenic	not provided	2015-10-13	criteria provided, single submitter	clinical testing	The M818L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution alters a conserved position predicted to be within the third transmembrane domain of the GRIN2B protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, the M818L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001172330	SCV001335356	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).