Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001985137 | SCV002223652 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with serine at codon 464 of the PIGO protein (p.Ile464Ser). The isoleucine residue is weakly conserved and there is a large physicochemical difference between isoleucine and serine. This variant is not present in population databases (ExAC no frequency). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). 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. |
| Ambry Genetics | RCV004043726 | SCV005005601 | uncertain significance | Inborn genetic diseases | 2023-11-22 | criteria provided, single submitter | clinical testing | The c.1391T>G (p.I464S) alteration is located in exon 7 (coding exon 6) of the PIGO gene. This alteration results from a T to G substitution at nucleotide position 1391, causing the isoleucine (I) at amino acid position 464 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |