ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.2248G>T (p.Ala750Ser) (rs139950099)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000311437 SCV000346076 uncertain significance Glycogen storage disease type III 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000423215 SCV000524779 uncertain significance not provided 2020-10-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Invitae RCV000311437 SCV000752137 uncertain significance Glycogen storage disease type III 2019-12-02 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 750 of the AGL protein (p.Ala750Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs139950099, ExAC 0.03%). This variant has not been reported in the literature in individuals with a AGL-related disease. ClinVar contains an entry for this variant (Variation ID: 291337). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on AGL function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV000311437 SCV001457979 uncertain significance Glycogen storage disease type III 2020-01-17 no assertion criteria provided clinical testing

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