Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000195424 | SCV000250741 | uncertain significance | not provided | 2018-03-09 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the SLC2A10 gene. Although the D468N variant has not been published as pathogenic or been reported as benign to our knowledge, it has been observed in three other individuals referred for Marfan/TAAD genetic testing at GeneDx, although a second variant in the SLC2A10 gene was not identified in any of these individuals. This variant is observed in 3/33,582 (0.01%) alleles from individuals of Latino ancestry in large population cohorts (Lek et al., 2016). The D468N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Nevertheless, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. |
| Invitae | RCV000644029 | SCV000765717 | uncertain significance | Arterial tortuosity syndrome | 2022-05-10 | 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. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 468 of the SLC2A10 protein (p.Asp468Asn). This variant is present in population databases (rs768345011, 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: 213750). 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. |
| Ambry Genetics | RCV002390520 | SCV002702434 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-08-30 | criteria provided, single submitter | clinical testing | The p.D468N variant (also known as c.1402G>A), located in coding exon 3 of the SLC2A10 gene, results from a G to A substitution at nucleotide position 1402. The aspartic acid at codon 468 is replaced by asparagine, 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. |