Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000009053 | SCV004298058 | pathogenic | Inherited glutathione synthetase deficiency | 2023-07-07 | criteria provided, single submitter | clinical testing | Experimental studies have shown that this missense change affects GSS function (PMID: 8896573, 10861239, 30581542). 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 GSS protein function. ClinVar contains an entry for this variant (Variation ID: 8527). This missense change has been observed in individual(s) with glutathione synthetase deficiency (PMID: 8896573, 11445798). This variant is present in population databases (rs121909308, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 267 of the GSS protein (p.Arg267Trp). This variant disrupts the p.Arg267 amino acid residue in GSS. Other variant(s) that disrupt this residue have been observed in individuals with GSS-related conditions (PMID: 31198081), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000009053 | SCV000029270 | pathogenic | Inherited glutathione synthetase deficiency | 1996-11-01 | no assertion criteria provided | literature only |