Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001045188 | SCV001209025 | uncertain significance | Glycogen storage disease type III | 2022-09-13 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 273 of the AGL protein (p.Ala273Gly). This variant is not present in population databases (gnomAD no frequency). 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: 842722). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt AGL protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. |
Illumina Laboratory Services, |
RCV001045188 | SCV001258802 | 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. |
Genome- |
RCV001045188 | SCV002055085 | uncertain significance | Glycogen storage disease type III | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002552577 | SCV003630233 | uncertain significance | Inborn genetic diseases | 2022-07-13 | criteria provided, single submitter | clinical testing | The c.818C>G (p.A273G) alteration is located in exon 6 (coding exon 5) of the AGL gene. This alteration results from a C to G substitution at nucleotide position 818, causing the alanine (A) at amino acid position 273 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Natera, |
RCV001045188 | SCV002091461 | uncertain significance | Glycogen storage disease type III | 2020-10-29 | no assertion criteria provided | clinical testing |