Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000197611 | SCV000250719 | uncertain significance | not provided | 2016-06-14 | criteria provided, single submitter | clinical testing | The R293H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R293H variant was not observed in approximately 6,500 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 R293H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. However, a missense mutation in a nearby residue (A283G) has been reported in association with a TAAD-related phenotype, supporting the functional importance of this region of the protein. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. |
| Invitae | RCV000644030 | SCV000765718 | uncertain significance | Arterial tortuosity syndrome | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 293 of the SLC2A10 protein (p.Arg293His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 213731). 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. 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 | RCV002372175 | SCV002687268 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-10-19 | criteria provided, single submitter | clinical testing | The p.R293H variant (also known as c.878G>A), located in coding exon 2 of the SLC2A10 gene, results from a G to A substitution at nucleotide position 878. The arginine at codon 293 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |