Submissions for variant NM_001134407.3(GRIN2A):c.1642G>C (p.Ala548Pro)

dbSNP: rs1057523843

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000441942	SCV000533503	likely pathogenic	not provided	2016-11-17	criteria provided, single submitter	clinical testing	The A548P 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. The A548P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts the A548P variant is probably damaging to the protein structure/function. Additionally, different missense variants at the same codon (A548T) and in a nearby residue (R552R) have been reported in association with Landau-Kleffner syndrome and intellectual disability, respectively (Lesca et al., 2013; Stenson et al., 2014). Therefore, the A548P variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001782905	SCV002026441	likely pathogenic	Landau-Kleffner syndrome	2019-01-01	criteria provided, single submitter	research