Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002008382 | SCV002268056 | likely pathogenic | Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 | 2021-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 611 of the GRIN2B protein (p.Gly611Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gly611 amino acid residue in GRIN2B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28377535, 31429998). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 GRIN2B protein function. This variant has been observed in individual(s) with clinical features of GRIN2B-related conditions (Invitae). |