Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520440 | SCV000620662 | uncertain significance | not provided | 2017-09-13 | criteria provided, single submitter | clinical testing | The H206Q variant in the PYGM gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The H206Q variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The H206Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Histidine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret H206Q as a variant of uncertain significance. |
Invitae | RCV001829517 | SCV003521880 | uncertain significance | Glycogen storage disease, type V | 2022-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 206 of the PYGM protein (p.His206Gln). This variant is present in population databases (rs371343340, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with PYGM-related conditions. ClinVar contains an entry for this variant (Variation ID: 451901). 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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. |
Revvity Omics, |
RCV001829517 | SCV003818078 | uncertain significance | Glycogen storage disease, type V | 2019-06-07 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001829517 | SCV002092339 | uncertain significance | Glycogen storage disease, type V | 2020-08-17 | no assertion criteria provided | clinical testing |