Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Neuberg Centre For Genomic Medicine, |
RCV000415279 | SCV004048055 | likely pathogenic | Glycogen storage disease type III | criteria provided, single submitter | clinical testing | The missense variant c.4353G>T (p.Trp1451Cys) in AGL gene has been reported in individuals affected with Glycogen storage disease type III (Perveen et al., 2020) and IEM (Alfadhel et al., 2016). This variant is reported with the allele frequency (0.001%) in the gnomAD and novel in 1000 genome database. It has been submitted to ClinVar with varying interpretations: Pathogenic/ Likely Pathogenic. The amino acid Trp at position 1451 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Trp1451Cys in AGL is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. | |
| Labcorp Genetics |
RCV000415279 | SCV004291955 | pathogenic | Glycogen storage disease type III | 2023-10-23 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 1451 of the AGL protein (p.Trp1451Cys). This variant is present in population databases (rs775685508, gnomAD 0.01%). This missense change has been observed in individual(s) with glycogen storage disease (PMID: 27629047, 32222031). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 374339). 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 expected to disrupt AGL protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| Center for Genomic Medicine, |
RCV000415279 | SCV004806020 | likely pathogenic | Glycogen storage disease type III | 2024-03-25 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000415279 | SCV000328819 | likely pathogenic | Glycogen storage disease type III | 2014-08-19 | no assertion criteria provided | clinical testing | Our laboratory has reported dual molecular diagnoses in AGL (NM_000028.2, c.4353G>T) and PCCA (NM_000282.3, c.425G>A) in this individual who has reported features of delayed motor milestones, delayed speech, hypotonia, short stature, failure to thrive, hepatomegaly, and elevated liver enzymes. |
| Biochemical Molecular Genetic Laboratory, |
RCV000415279 | SCV001190751 | pathogenic | Glycogen storage disease type III | 2020-02-05 | no assertion criteria provided | clinical testing |