Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001368141 | SCV001564523 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with histidine at codon 689 of the PIGO protein (p.Arg689His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs771748735, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with PIGO-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | RCV002550073 | SCV003709955 | uncertain significance | Inborn genetic diseases | 2021-06-15 | criteria provided, single submitter | clinical testing | The c.2066G>A (p.R689H) alteration is located in exon 7 (coding exon 6) of the PIGO gene. This alteration results from a G to A substitution at nucleotide position 2066, causing the arginine (R) at amino acid position 689 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |