Table 1.
The GluD1 M3 domain is more tolerant to variation than GluD2.
| Gene | Nucleotide Change | Protein Change | Domain | PolyPhen | gnomAD Alleles | gnomAD noneuro Alleles | SCHEMA Case Alleles | SCHEMA Control Alleles | Source |
|---|---|---|---|---|---|---|---|---|---|
| GRID1 | c.1911G > T | p.Trp637Cys | M3 | probably damaging | 2/248 908 | 2/206 130 | 1/48 496 | 2/194 644 | ClinVar |
| GRID1 | c.1940C > T | p.Ser647Phe | M3 | probably damaging | 3/249 524 | 2/206 728 | 0 | 1/194 644 | gnomAD v2.1.1 |
| GRID1 | c.1946C > T | p.Thr649Ile | M3 | probably damaging | 1/249 506 | 0 | 0 | 1/194 644 | gnomAD v2.1.1 |
| GRID1 | c.1948G > A | p.Ala650Thr | M3 | probably damaging | 1/249 224 | 0 | 1/48 496 | 0 | SCHEMA/gnomAD v2.1.1 |
| GRID1 | c.1952A > G | p.Asn651Ser | M3 | benign | 6/249 322 | 6/206 636 | 0 | 3/194 644 | gnomAD v2.1.1 |
| GRID2 | c.1936 T > C | p.Ser646Pro | M3 | probably damaging | 0 | 0 | 0 | 0 | ClinVar |
| GRID2 | c.1945A > G | p.Thr649Ala | M3 | probably damaging | 0 | 0 | 0 | 0 | This study |
| GRID2 | c.1945A > T | p.Thr649Ser | M3 | probably damaging | 0 | 0 | 0 | 0 | ClinVar |
| GRID2 | c.1946C > T | p.Thr649Met | M3 | probably damaging | 22/281 822 | 19/228 708 | 0 | 0 | gnomAD v2.1.1 |
| GRID2 | c.1948G > C | p.Ala650Pro | M3 | probably damaging | 0 | 0 | 0 | 0 | ClinVar |
| GRID2 | c.1949C > T | p.Ala650Val | M3 | probably damaging | 0 | 0 | 0 | 0 | ClinVar |
| GRID2 | c.1961C > G | p.Ala654Gly | M3 | probably damaging | 0 | 0 | 0 | 0 | ClinVar |
| GRID2 | c.1960G > A | p.Ala654Thr | M3 | probably damaging | 0 | 0 | 0 | 0 | Coutelier et al. [41] |
| GRID2 | c.1961C > A | p.Ala654Asp | M3 | probably damaging | 0 | 0 | 0 | 0 | Coutelier et al. [41] |
| GRID2 | c.1966C > G | p.Leu656Val | M3-S2 | probably damaging | 0 | 0 | 0 | 0 | Coutelier et al. [41] |
Nucleotide and protein changes are represented as the consequence on the canonical NCBI RefSeq for GRID1 (NM_017551.2) and GRID2 (NM_001510.4). A complete list of GRID1 and GRID2 variants with clinical information is given in Supplementary Tables S2 and S3. Variants present in ClinVar are summarized in Supplementary Tables S4 and S5. All variants were predicted by SIFT to be deleterious (not shown).