Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000796946 | SCV000936481 | uncertain significance | Arterial tortuosity syndrome | 2021-09-15 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs760437795, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with SLC2A10-related conditions. This sequence change replaces arginine with proline at codon 516 of the SLC2A10 protein (p.Arg516Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline. This variant also falls at the last nucleotide of exon 4, which is part of the consensus splice site for this exon. 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). |