Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000247680 | SCV000319242 | uncertain significance | Cardiovascular phenotype | 2014-02-26 | criteria provided, single submitter | clinical testing | ​The p.Q363E variant (also known as c.1087C>G), located in coding exon 2 of the SLC2A10 gene, results from a C to G substitution at nucleotide position 1087. The glutamine at codon 363 is replaced by glutamic acid, an amino acid with some similar properties. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. Based on protein sequence alignment, this amino acid position is not conserved in available vertebrate species, and glutamic acid is the reference amino acid in rabbit and pika. 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 variant remains unclear. |
| Invitae | RCV000805423 | SCV000945379 | uncertain significance | Arterial tortuosity syndrome | 2018-07-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with glutamic acid at codon 363 of the SLC2A10 protein (p.Gln363Glu). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SLC2A10-related disease. ClinVar contains an entry for this variant (Variation ID: 263820). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |