Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000704255 | SCV000833197 | uncertain significance | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome | 2019-02-22 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function 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 with PURA-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with serine at codon 165 of the PURA protein (p.Gly165Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. 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. |
Undiagnosed Diseases Network, |
RCV000704255 | SCV001245597 | likely pathogenic | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome | 2019-03-02 | criteria provided, single submitter | clinical testing | Structural biology analysis predicts missense change will be damaging to protein function |
Baylor Genetics | RCV000704255 | SCV001520922 | likely pathogenic | PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome | 2019-03-02 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |