Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521540 | SCV000618516 | uncertain significance | not provided | 2017-06-13 | criteria provided, single submitter | clinical testing | The G266V variant of uncertain significance in the SLC2A10 gene has not been published as pathogenic or been reported as benign to our knowledge. G266V is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function, G266V is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In addition, this substitution occurs at a position that is not conserved, where V266 is the wild-type residue in at least two species. Finally, no pathogenic missense variants in nearby residues have been reported in the Human Gene Mutation Database (Stenson et al., 2014), indicating that this region of the gene is not known to harbor disease-causing variants. |
| Invitae | RCV001316953 | SCV001507595 | uncertain significance | Arterial tortuosity syndrome | 2022-03-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 266 of the SLC2A10 protein (p.Gly266Val). This variant is present in population databases (rs369484751, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SLC2A10-related conditions. ClinVar contains an entry for this variant (Variation ID: 449995). 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 SLC2A10 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Ambry Genetics | RCV002420311 | SCV002677205 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-12-02 | criteria provided, single submitter | clinical testing | The p.G266V variant (also known as c.797G>T), located in coding exon 2 of the SLC2A10 gene, results from a G to T substitution at nucleotide position 797. The glycine at codon 266 is replaced by valine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV001316953 | SCV003835764 | uncertain significance | Arterial tortuosity syndrome | 2022-10-16 | criteria provided, single submitter | clinical testing |