Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000255971 | SCV000322540 | uncertain significance | not provided | 2016-02-22 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the GRIN1 gene. The D169N 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 occurs at a position that is conserved in mammals. In addition, the D169N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with GRIN1-related disease. (Stenson et al., 2014) In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV001313303 | SCV001503795 | uncertain significance | Intellectual disability, autosomal dominant 8 | 2022-05-05 | criteria provided, single submitter | clinical testing | 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. 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 expected to disrupt GRIN1 protein function. ClinVar contains an entry for this variant (Variation ID: 265555). This variant has not been reported in the literature in individuals affected with GRIN1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 169 of the GRIN1 protein (p.Asp169Asn). |