ClinVar Miner

Submissions for variant NM_000642.3(AGL):c.4221del (p.Lys1407fs) (rs786204655)

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Total submissions: 3
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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 RCV000780821 SCV000918400 pathogenic Glycogen storage disease type III 2017-11-20 criteria provided, single submitter clinical testing Variant summary: The AGL c.4221delA (p.Lys1407AsnfsX8) variant results in a premature termination codon, predicted to cause a truncated or absent AGL protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.4529dupA, p.Tyr1510X). One in silico tool predicts a damaging outcome for this variant. The variant has been reported in affected individuals in the literature who carry second pathogenic variants and have <10% WT level of AGL enzyme activity (Paesold-Burda_2007, Crushell_2010). This variant is absent in 246038 control chromosomes. Taken together, this variant is classified as pathogenic.
Mendelics RCV000780821 SCV001135380 pathogenic Glycogen storage disease type III 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV000780821 SCV001396803 pathogenic Glycogen storage disease type III 2019-07-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys1407Asnfs*8) in the AGL gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with glycogen storage disease type III (PMID: 17994282, 20490926). ClinVar contains an entry for this variant (Variation ID: 633033). Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic.

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