ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.4379G>A (p.Arg1460His)

gnomAD frequency: 0.00001  dbSNP: rs546855663
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001057749 SCV001222258 uncertain significance Glycogen storage disease type III 2022-07-30 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1460 of the AGL protein (p.Arg1460His). This variant is present in population databases (rs546855663, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with AGL-related conditions. ClinVar contains an entry for this variant (Variation ID: 853019). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Fulgent Genetics, Fulgent Genetics RCV001057749 SCV002816296 uncertain significance Glycogen storage disease type III 2021-09-16 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001057749 SCV004050096 uncertain significance Glycogen storage disease type III 2023-04-11 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV001057749 SCV004100437 uncertain significance Glycogen storage disease type III criteria provided, single submitter clinical testing The missense variant p.R1460H in AGL (NM_000642.3) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.R1460H variant is observed in 2/978 (0.2045%) alleles from individuals of South Asian background in 1000 Genomes, which is greater than expected for the disorder.The p.R1460H missense variant is predicted to be damaging by both SIFT and PolyPhen2. The histidine residue at codon 1460 of AGL is only present in a single other mammalian species: Squirrel. The nucleotide c.4379 in AGL is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.
Natera, Inc. RCV001057749 SCV002094590 uncertain significance Glycogen storage disease type III 2021-04-19 no assertion criteria provided clinical testing

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