Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000197067 | SCV000250716 | uncertain significance | not provided | 2015-04-21 | criteria provided, single submitter | clinical testing | p.Leu148Pro (L148P) CTG>CCG: c.443 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 L148P variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The L148P variant was not observed in approximately 6500 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 L148P 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 where amino acids with similar properties to Leucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Finally, a missense mutation in a nearby residue (G142V) has been reported in association with arterial tortuosity syndrome, supporting the functional importance of this region of the protein. 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 TAADV2-1 |
| Invitae | RCV001853163 | SCV002146352 | uncertain significance | Arterial tortuosity syndrome | 2020-12-25 | 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. 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. This variant has not been reported in the literature in individuals with SLC2A10-related conditions. ClinVar contains an entry for this variant (Variation ID: 213728). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 148 of the SLC2A10 protein (p.Leu148Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |