ClinVar Miner

Submissions for variant NM_000027.4(AGA):c.800dup (p.Pro268fs) (rs386833436)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000000249 SCV000485780 likely pathogenic Aspartylglucosaminuria 2016-02-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000000249 SCV000918397 pathogenic Aspartylglucosaminuria 2018-04-11 criteria provided, single submitter clinical testing Variant summary: AGA c.800dupT (p.Pro268AlafsX52) 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. The variant was observed with an allele freqyency of 2.8e-05 in 246258 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in AGA causing Aspartylglucosaminuria (2.8e-05 vs 0.0049), allowing no conclusion about variant significance. The variant, c.800dupT, has been reported in the literature in a homozygous individual affected with Aspartylglucosaminuria, who presented with less than 10% normal AGA activity (Ikonen_1991). These data indicate that the variant may be associated with disease. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as "likely pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV000000249 SCV001415728 pathogenic Aspartylglucosaminuria 2019-07-05 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the AGA gene (p.Pro268Alafs*52). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 79 amino acids of the AGA protein. This variant is present in population databases (rs386833436, ExAC 0.02%). This variant has been observed in an individual affected with aspartylglucosaminuria (PMID: 1722323). ClinVar contains an entry for this variant (Variation ID: 225). This variant has been reported to affect AGA protein function (PMID: 1722323, 11309371). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000249 SCV000020393 pathogenic Aspartylglucosaminuria 1991-12-15 no assertion criteria provided literature only
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000000249 SCV000081796 probable-pathogenic Aspartylglucosaminuria no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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