Submissions for variant NM_000642.3(AGL):c.4506_4510del (p.Glu1502fs)

dbSNP: rs1064795728

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000482459	SCV000571808	likely pathogenic	not provided	2016-10-10	criteria provided, single submitter	clinical testing	The c.4506_4510delACTGA variant in the AGL gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant causes a frameshift starting with codon Glutamic Acid 1502, changes this amino acid to an Aspartic Acid residue, and creates a premature Stop codon at position 3 of the new reading frame, denoted p.Glu1502AspfsX3. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 31 amino acids of the protein are replaced with 2 incorrect amino acids. The c.4506_4510delACTGA variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The c.4506_4510delACTGA variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae	RCV003633509	SCV004408981	pathogenic	Glycogen storage disease type III	2022-11-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1502Aspfs*3) in the AGL gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 31 amino acid(s) of the AGL protein. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the AGL protein in which other variant(s) (p.Tyr1510*) have been determined to be pathogenic (PMID: 8990006, 20071996, 20490926, 23430490). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 422357). This variant has not been reported in the literature in individuals affected with AGL-related conditions. This variant is not present in population databases (gnomAD no frequency).