Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001214818 | SCV001386523 | uncertain significance | Hyperphosphatasia with intellectual disability syndrome 2 | 2021-09-26 | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PIGO-related conditions. This variant is present in population databases (rs771571749, ExAC 0.002%). This sequence change replaces tyrosine with cysteine at codon 301 of the PIGO protein (p.Tyr301Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. |
Gene |
RCV002275321 | SCV002562594 | uncertain significance | not provided | 2022-02-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24417746) |