Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003496300 | SCV004263145 | uncertain significance | RFT1-congenital disorder of glycosylation | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 152 of the RFT1 protein (p.Lys152Asn). This variant also falls at the last nucleotide of exon 4, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RFT1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. This variant disrupts the p.Lys152 amino acid residue in RFT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19701946, 19856127, 26892341, 27172925). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |