Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000195523 | SCV000252107 | likely pathogenic | not provided | 2014-07-24 | criteria provided, single submitter | clinical testing | The R192Q variant that is likely pathogenic was identified in the PNPT1 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R192Q 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 that is highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in MITONUC-MITOP panel(s). |
| Invitae | RCV000195523 | SCV002154703 | uncertain significance | not provided | 2023-02-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 192 of the PNPT1 protein (p.Arg192Gln). This variant is present in population databases (rs772153760, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PNPT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 215006). 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 PNPT1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |