Submissions for variant NM_000642.3(AGL):c.4422del (p.Ala1475fs)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001193899	SCV001363065	likely pathogenic	Glycogen storage disease type III	2019-09-16	criteria provided, single submitter	clinical testing	Variant summary: AGL c.4422delT (p.Ala1475GlnfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A truncation downstream of this position has been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250766 control chromosomes (gnomAD). c.4422delT has been reported in the literature in an individual affected with Glycogen Storage Disease Type III (Goldstein_2010). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001193899	SCV001392685	pathogenic	Glycogen storage disease type III	2025-01-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ala1475Glnfs*4) in the AGL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). This variant is present in population databases (no rsID available, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with clinical features of glycogen storage disease type III (PMID: 20648714). ClinVar contains an entry for this variant (Variation ID: 929046). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV001193899	SCV002055512	pathogenic	Glycogen storage disease type III	2021-07-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001193899	SCV004190950	pathogenic	Glycogen storage disease type III	2023-01-28	criteria provided, single submitter	clinical testing

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