Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clinical Genetics Laboratory, |
RCV000656662 | SCV000778540 | uncertain significance | RFT1 related CDG | 2018-06-20 | criteria provided, single submitter | clinical testing | This variant has been found in heterozygous state previously at low frequency in healthy individuals of ExAC[0.00003/4], 1000Genome[0.0002/1] and inhouse database[2 individuals] and never in homozygous state. This variant lies in the transmembrane helical domain. insilico analyses tools predicted this variant as follow SIFT-damaging PROVEAN-deleterious POLYPHEN-probably damaging MUTATION TASTER- disease causing, unaffected Parents are heterozygous for the same variant |
| Invitae | RCV001855350 | SCV002316218 | uncertain significance | RFT1-congenital disorder of glycosylation | 2024-01-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 340 of the RFT1 protein (p.Gly340Ser). This variant is present in population databases (rs568474177, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of RFT1-congenital disorder of glycosylation (PMID: 30071302). ClinVar contains an entry for this variant (Variation ID: 545641). 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 RFT1 protein function with a negative predictive value of 80%. 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. |