ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.745T>C (p.Ser249Pro)

gnomAD frequency: 0.00001  dbSNP: rs1386718298
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Total submissions: 5
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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.
GeneDx 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-Nilou Lab RCV000707045 SCV002027237 uncertain significance Glycogen storage disease, type II 2021-09-05 criteria provided, single submitter clinical testing
Revvity Omics, Revvity 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.

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