Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001370388 | SCV001566865 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2022-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 350 of the PIGO protein (p.Gly350Ala). This variant is present in population databases (rs368691880, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PIGO-related conditions. ClinVar contains an entry for this variant (Variation ID: 1060892). 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 PIGO protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. |
| Gene |
RCV001751729 | SCV001987584 | uncertain significance | not provided | 2019-06-25 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |