Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000707045 | SCV000836125 | uncertain significance | Glycogen storage disease, type II | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with proline at codon 249 of the GAA protein (p.Ser249Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with GAA-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |
Gene |
RCV001766565 | SCV001998966 | uncertain significance | not provided | 2019-09-09 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Genome- |
RCV000707045 | SCV002027237 | uncertain significance | Glycogen storage disease, type II | 2021-09-05 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001766565 | SCV003828459 | uncertain significance | not provided | 2022-04-08 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003165928 | SCV003857463 | uncertain significance | Cardiovascular phenotype | 2023-02-15 | criteria provided, single submitter | clinical testing | The p.S249P variant (also known as c.745T>C), located in coding exon 3 of the GAA gene, results from a T to C substitution at nucleotide position 745. The serine at codon 249 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |