ClinVar Miner

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

dbSNP: rs786204655
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Total submissions: 5
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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 2023-07-24 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. Loss-of-function variants in AGL are known to be pathogenic (PMID: 19299494). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 633033). This premature translational stop signal has been observed in individual(s) with glycogen storage disease type III (PMID: 17994282, 20490926). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database.
Genome-Nilou Lab RCV000780821 SCV002055510 pathogenic Glycogen storage disease type III 2021-07-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV000780821 SCV004211257 pathogenic Glycogen storage disease type III 2023-07-19 criteria provided, single submitter clinical testing

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