Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002311998 | SCV000846979 | uncertain significance | Inborn genetic diseases | 2016-06-16 | criteria provided, single submitter | clinical testing | The p.S1216T variant (also known as c.3647G>C), located in coding exon 12 of the GRIN2A gene, results from a G to C substitution at nucleotide position 3647. The serine at codon 1216 is replaced by threonine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs367543134. This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. In the ESP, this variant was not observed in 6497 samples (12994 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
| Invitae | RCV003764782 | SCV004661748 | uncertain significance | Landau-Kleffner syndrome | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1216 of the GRIN2A protein (p.Ser1216Thr). This variant is present in population databases (rs367543134, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with GRIN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 98463). 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 not expected to disrupt GRIN2A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Psychiatry Genetics Yale University | RCV000084754 | SCV000116890 | not provided | not provided | no assertion provided | not provided |