ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.334A>G (p.Ile112Val) (rs147024351)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000299112 SCV000346056 uncertain significance Glycogen storage disease type III 2018-01-13 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.
Invitae RCV000299112 SCV000626726 likely benign Glycogen storage disease type III 2020-12-04 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000299112 SCV000845641 likely benign Glycogen storage disease type III 2018-08-07 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786275 SCV000925030 uncertain significance not provided 2017-11-07 no assertion criteria provided provider interpretation p.Ile112Val (c.334A>G) in exon 4 of the AGL gene (NM_000642.2; chr1-100327853-A-G) - SCICD classification: variant of uncertain significance, likely benign SCICD Classification: variant of uncertain significance, likely benign based on mode of inheritance (must be autosomal recessive to cause disease), relatively high frequency in the general population and lack of case data. We do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). Lab Classification (Invitae): variant of uncertain significance Gene-level evidence: AGL: The AGL gene encodes the glycogen debrancher enzyme. Deficiency of this enzyme causes glycogen storage disease IIIb (GSDIII aka Cori disease). This is an autosomal recessive disorder with a spectrum of manifestations that include hypoglycemia, hyperlipidemia, hepatic dysfunction. Some individuals have neuromuscular disease and cardiomyopathy. A person with a single disease causing variant is a carrier and two disease-causing variants lead to clinical manifestations. Case data (not including our patient): Our patient does not have inherited cardiovascular disease per evaluation. Patient was referred to our lab due to another pathogenic MYBPC3 variant identified via 23andMe and Promethease data. We sent a panel. The variant in MYBPC3 did not clinically confirm. ClinVar: Illumina Clinical labs - no details provided Cases in the literature: This variant is mentioned in a textbook by Wyandt, called Human Chromosome Variation. This individual had glycogen storage disease III and the authors classified this variant as a VUS. Segregation data: none reported Functional data: none reported In silico data (missense variants only): Per the test report, "Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"." Conservation data: The isoleucine at codon 112 is not conserved across species. A valine is present in many other species. Neighboring amino acids are completely conserved. Nearby pathogenic variants at this codon or neighboring codons: A synonymous variant is present at a nearby residue, p.Tyr106Tyr and is classified as a VUS by Illumina Clinical labs. No Population data: Highest MAF in European population: 0.1%. The variant was reported online in 187 of 136,607 individuals in the Genome Aggregation Consortium Dataset (gnomAD;, which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Ashkenazi, Latino descent. Specifically, the variant was observed in 153 of 63,354 individuals of European descent (MAF=0.1%), 23 of 15,391 individuals of South Asian descent, 4 of 12,016 individuals of African descent, 3 of 17,210 individuals of Latino descent, 1 of 12,895 individuals of Finnish descent and 3 of 3231 individuals of "other" descent. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease.
Natera, Inc. RCV000299112 SCV001452901 uncertain significance Glycogen storage disease type III 2020-01-10 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.