Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000807388 | SCV000947436 | uncertain significance | Glycogen storage disease IXa1 | 2018-12-26 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Tyr116 amino acid residue in PHKA2. Another variant that disrupts this residue has been observed in affected individuals (PMID: 9870210), which suggests that this may be a clinically significant amino acid residue. 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 been observed in an individual affected with glycogen storage disease and shown to segregate in the family (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with asparagine at codon 116 of the PHKA2 protein (p.Tyr116Asn). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and asparagine. 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. |