Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000539170 | SCV000652673 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2022-10-18 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 428 of the PIGO protein (p.Leu428Gln). This variant is present in population databases (rs182396158, gnomAD 0.06%). 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: 473214). 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. 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 | RCV002530209 | SCV003730595 | uncertain significance | Inborn genetic diseases | 2021-03-25 | criteria provided, single submitter | clinical testing | The c.1283T>A (p.L428Q) alteration is located in exon 7 (coding exon 6) of the PIGO gene. This alteration results from a T to A substitution at nucleotide position 1283, causing the leucine (L) at amino acid position 428 to be replaced by a glutamine (Q). The in silico prediction for the p.L428Q alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |