Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001344846 | SCV001538928 | uncertain significance | Syndromic X-linked intellectual disability 14 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 368 of the UPF3B protein (p.Arg368Trp). This variant is present in population databases (rs374676402, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with UPF3B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1041099). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on UPF3B protein function. 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. |
Ambry Genetics | RCV002431971 | SCV002740570 | uncertain significance | Inborn genetic diseases | 2018-05-17 | criteria provided, single submitter | clinical testing | The p.R368W variant (also known as c.1102C>T), located in coding exon 10 of the UPF3B gene, results from a C to T substitution at nucleotide position 1102. The arginine at codon 368 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |