Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV001141334 | SCV001301675 | uncertain significance | Arterial tortuosity syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Ambry Genetics | RCV002339416 | SCV002644585 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-09-30 | criteria provided, single submitter | clinical testing | The p.M167I variant (also known as c.501G>A), located in coding exon 2 of the SLC2A10 gene, results from a G to A substitution at nucleotide position 501. The methionine at codon 167 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001141334 | SCV003273535 | uncertain significance | Arterial tortuosity syndrome | 2022-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 167 of the SLC2A10 protein (p.Met167Ile). 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. 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 expected to disrupt SLC2A10 protein function. ClinVar contains an entry for this variant (Variation ID: 897833). This variant has not been reported in the literature in individuals affected with SLC2A10-related conditions. This variant is present in population databases (rs763979126, gnomAD 0.003%). |