Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000696650 | SCV000825219 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2021-02-03 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with PIGO-related disease. This variant is present in population databases (rs762970543, ExAC 0.01%). This sequence change replaces glycine with alanine at codon 261 of the PIGO protein (p.Gly261Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine. |
Gene |
RCV001766505 | SCV001990839 | uncertain significance | not provided | 2019-04-04 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |