Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002311225 | SCV000320603 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2015-12-30 | criteria provided, single submitter | clinical testing | The p.V123M variant (also known as c.367G>A), located in coding exon 2 of the SLC2A10 gene, results from a G to A substitution at nucleotide position 367. The valine at codon 123 is replaced by methionine, an amino acid with highly similar properties. Based on data from ExAC, the A allele was reported in 1 of 121248 (0.0008%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed December 28, 2015]). 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. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species, and methionine is the reference amino acid in two 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 variant remains unclear. |
| Invitae | RCV001217868 | SCV001389726 | uncertain significance | Arterial tortuosity syndrome | 2022-04-20 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 123 of the SLC2A10 protein (p.Val123Met). This variant is present in population databases (rs770619266, gnomAD 0.009%). 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: 264583). 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. |
| Ce |
RCV002059051 | SCV002496678 | uncertain significance | not provided | 2022-03-01 | criteria provided, single submitter | clinical testing |