Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001213747 | SCV001385396 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2019-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 454 of the PIGO protein (p.Gly454Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs751477063, ExAC 0.006%). This variant has not been reported in the literature in individuals with PIGO-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |