Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000196340 | SCV000250727 | uncertain significance | not specified | 2014-08-22 | criteria provided, single submitter | clinical testing | p.Ser463Arg (AGC>CGC): c.1387 A>C in exon 3 of the SLC2A10 gene (NM_030777.3). A variant of unknown significance has been identified in the SLC2A10 gene. The S463R variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The S463R 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. The S463R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved within mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have not been reported, indicating this region of the protein may tolerate 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 |
| Labcorp Genetics |
RCV000795533 | SCV000934998 | uncertain significance | Arterial tortuosity syndrome | 2022-02-03 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SLC2A10-related conditions. This variant is present in population databases (rs771091234, gnomAD 0.0009%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 463 of the SLC2A10 protein (p.Ser463Arg). ClinVar contains an entry for this variant (Variation ID: 213738). 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. |