Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001370202 | SCV001566669 | uncertain significance | Glycogen storage disease, type VI | 2020-01-13 | 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 with PYGL-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 213 of the PYGL protein (p.Gly213Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |
Neuberg Centre For Genomic Medicine, |
RCV001370202 | SCV004176479 | uncertain significance | Glycogen storage disease, type VI | 2023-03-01 | criteria provided, single submitter | clinical testing | The missense variant c.637G>A (p.Gly213Arg) in the PYGL gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency (0.0003%) in the gnomAD Exomes and novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Glycine at position 213 is changed to a Arginine changing protein sequence and it might alter its composition and physico- chemical properties. The amino acid change p.Gly213Arg in PYGL is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |