Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000658454 | SCV000780226 | likely pathogenic | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the GRIN2B gene. The N817S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N817S variant is not observed in large population cohorts (Lek et al., 2016). In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Missense variants in nearby residues have been reported in the Human Gene Mutation Database in individuals with GRIN2B-related disorders (Stenson et al., 2014). However, the N817S 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. |
| Baylor Genetics | RCV000680004 | SCV000807442 | uncertain significance | Developmental and epileptic encephalopathy, 27 | 2017-09-01 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it once in our laboratory de novo in a 4-year-old male with severe delays, prfound hypotonia, history of spasticity, infantile spasms, hand flapping, dysmorphisms, failure to thrive, global brain volume loss |
| Ambry Genetics | RCV002424558 | SCV002731558 | uncertain significance | Inborn genetic diseases | 2020-10-13 | criteria provided, single submitter | clinical testing | The p.N817S variant (also known as c.2450A>G), located in coding exon 11 of the GRIN2B gene, results from an A to G substitution at nucleotide position 2450. The asparagine at codon 817 is replaced by serine, an amino acid with highly similar properties. 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 alteration remains unclear. |
| Baylor Genetics | RCV003152609 | SCV003841224 | likely pathogenic | Intellectual disability, autosomal dominant 6 | criteria provided, single submitter | clinical testing |