Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000798144 | SCV000937745 | pathogenic | Glycogen storage disease IXa1 | 2021-09-17 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with glycogen storage disease (PMID: 21646031, 22899091, 25070466, 28627441; Invitae). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg45 amino acid residue in PHKA2. Other variant(s) that disrupt this residue have been observed in individuals with PHKA2-related conditions (PMID: 28627441), 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with tryptophan at codon 45 of the PHKA2 protein (p.Arg45Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. |
Mendelics | RCV000798144 | SCV001141500 | likely pathogenic | Glycogen storage disease IXa1 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002272360 | SCV002558134 | likely pathogenic | not provided | 2022-07-29 | 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; This variant is associated with the following publications: (PMID: 28627441, 21646031, 23578772, 22899091, 28283841, 25070466, 31725618) |