Submissions for variant NM_001134407.3(GRIN2A):c.3884T>C (p.Ile1295Thr)

gnomAD frequency: 0.00004  dbSNP: rs757351084

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187667	SCV000241264	uncertain significance	not provided	2016-12-05	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the GRIN2A gene. The I1295T variant in the GRIN2A gene has been reported previously as a de novo variant in an individual with schizophrenia (Fromer et al., 2014). The I1295T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The I1295T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size, and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Laboratory Services, Illumina	RCV000406626	SCV000400140	likely benign	Landau-Kleffner syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000406626	SCV001235852	likely benign	Landau-Kleffner syndrome	2025-01-25	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000406626	SCV002048128	uncertain significance	Landau-Kleffner syndrome	2021-02-04	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000406626	SCV003817445	uncertain significance	Landau-Kleffner syndrome	2020-09-15	criteria provided, single submitter	clinical testing