ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.298C>A (p.Gln100Lys)

gnomAD frequency: 0.00001  dbSNP: rs780027584
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001992440 SCV002223545 uncertain significance Glycogen storage disease, type II 2021-09-24 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 100 of the GAA protein (p.Gln100Lys). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GAA-related conditions. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV001992440 SCV005908170 uncertain significance Glycogen storage disease, type II 2022-09-28 criteria provided, single submitter clinical testing The p.Gln100Lys variant in the GAA gene has not been previously reported in association with disease. This variant has been submitted to ClinVar (Variation ID: 1444789, ncbi.nlm.nih.gov/clinvar/) and has been identified in 1/248402 chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. In silico tools predict that the p.Gln100Lys variant does not impact protein function; however, these predictions have not been tested directly. Using ACMG guidelines, this variant was classified as a variant of uncertain significance (ACMG evidence codes used: PM2_supporting, BP4).

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