Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001267363 | SCV001445544 | uncertain significance | Inborn genetic diseases | 2020-06-11 | criteria provided, single submitter | clinical testing | The alteration results in an amino acid change:_x000D_ _x000D_ The c.3652T>A (p.C1218S) alteration is located in exon 13 (coding exon 12) of the GRIN2B gene. This alteration results from a T to A substitution at nucleotide position 3652, causing the cysteine (C) at amino acid position 1218 to be replaced by a serine (S). The alteration is not observed in population databases: _x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the GRIN2B c.3652T>A alteration was not observed, with coverage at this position. The altered amino acid is conserved throughout evolution:_x000D_ _x000D_ The p.C1218 amino acid is conserved in available higher vertebrate species, with poor alignment in available fish species. The alteration is predicted inconclusive by in silico modeling:_x000D_ _x000D_ The in silico prediction for the p.C1218S alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001880143 | SCV002220748 | uncertain significance | Intellectual disability, autosomal dominant 6; Developmental and epileptic encephalopathy, 27 | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 1218 of the GRIN2B protein (p.Cys1218Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GRIN2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 986115). 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 GRIN2B 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. |