Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001211126 | SCV001382651 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2019-10-08 | criteria provided, single submitter | clinical testing | 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This missense variant has been observed to segregate with clinical features of early infantile epileptic encephalopathy, developmental delay and near normal levels of alkaline phosphatase in a family (PMID:28900819). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 255 of the PIGO protein (p.Met255Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. |