Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000199334 | SCV000250740 | uncertain significance | not provided | 2014-09-11 | criteria provided, single submitter | clinical testing | p.Val332Ala (GTG>GCG): c.995 T>C in exon 2 of the SLC2A10 gene (NM_030777.3). A variant of unknown significance has been identified in the SLC2A10 gene. The V332A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The V332A 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. However, the V332A 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 predicts this variant likely does not alter the protein structure/function. Furthermore, no missense mutations in nearby residues have been reported in association with ATS, indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD |
| Invitae | RCV001343842 | SCV001537858 | uncertain significance | Arterial tortuosity syndrome | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 332 of the SLC2A10 protein (p.Val332Ala). This variant is present in population databases (rs570363463, gnomAD 0.003%). 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: 213749). 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. |