Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489014 | SCV000577825 | likely pathogenic | not provided | 2015-04-23 | criteria provided, single submitter | clinical testing | The G175R variant in the SLC2A1 gene has not been published as a variant, nor has it been reported as a benign polymorphism to our knowledge. The G175R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G175R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (L169P) has been reported in the Human Gene Mutation Database in association with glucose transported 1 deficiency syndrome (Stenson et al., 2014), supporting the functional importance of this region of the protein. The G175R variant is a strong candidate for a disease-causing variant however the possibility it may be a rare benign variant cannot be excluded |
| Labcorp Genetics |
RCV002298620 | SCV002592856 | uncertain significance | GLUT1 deficiency syndrome 1, autosomal recessive | 2022-08-31 | 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 SLC2A1 protein function. ClinVar contains an entry for this variant (Variation ID: 427185). This variant has not been reported in the literature in individuals affected with SLC2A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 175 of the SLC2A1 protein (p.Gly175Arg). |