Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000411544 | SCV000486904 | pathogenic | Glycogen storage disease type III | 2016-08-31 | criteria provided, single submitter | clinical testing | |
Centre for Human Genetics | RCV000411544 | SCV001482494 | pathogenic | Glycogen storage disease type III | 2020-06-15 | criteria provided, single submitter | clinical testing | disease causing |
Invitae | RCV000411544 | SCV001592637 | pathogenic | Glycogen storage disease type III | 2023-07-08 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 20 of the AGL gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs201201443, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with glycogen storage disease type III (PMID: 10472540, 31028654). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 371344). Studies have shown that disruption of this splice site results in skipping of exon 21, but is expected to preserve the integrity of the reading-frame (PMID: 10472540, 31028654). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000411544 | SCV002055489 | pathogenic | Glycogen storage disease type III | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000411544 | SCV002103550 | pathogenic | Glycogen storage disease type III | 2022-02-08 | criteria provided, single submitter | clinical testing | Variant summary: AGL c.2681+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 250950 control chromosomes. c.2681+1G>T has been reported in the literature in the homozygous state in siblings affected with Glycogen Storage Disease Type III (Goldstein_2010, Hijazi_2021, Paschall_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000411544 | SCV004211068 | pathogenic | Glycogen storage disease type III | 2023-09-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002524625 | SCV003574521 | uncertain significance | Inborn genetic diseases | 2021-10-29 | flagged submission | clinical testing | Resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNA decay Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |