ClinVar Miner

Submissions for variant NM_000030.3(AGXT):c.33del (p.Lys12fs) (rs180177201)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169102 SCV000220294 likely pathogenic Primary hyperoxaluria, type I 2014-05-01 criteria provided, single submitter literature only
Invitae RCV000794507 SCV000933919 pathogenic not provided 2018-10-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys12Argfs*34) in the AGXT gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed to be homozygous or in combination with another AGXT variant in individuals affected with hyperoxaluria (PMID: 15963748, 17495019, 26383609). ClinVar contains an entry for this variant (Variation ID: 188775). Loss-of-function variants in AGXT are known to be pathogenic (PMID: 19479957). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192774 SCV001361102 pathogenic Primary hyperoxaluria 2019-02-08 criteria provided, single submitter clinical testing Variant summary: AGXT c.33delC (p.Lys12ArgfsX34) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. p.Lys12fsX156, p.Ser275fsX38). The variant was absent in 242874 control chromosomes (gnomAD). c.33delC has been reported in the literature in homozygous individuals affected with Primary Hyperoxaluria Type 1 (Amoroso 2001, Williams 2007, Hoyer-Kuhn_2014). These data indicate that the variant is likely to be associated with disease. One of these publications also measured liver AGT activity in a homozygous patient, and demonstrated a pronounced variant effect, resulting in <10% of normal activity (Williams 2007). 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 pathogenic.
Clinical Biochemistry Laboratory,Health Services Laboratory RCV000169102 SCV000239728 pathogenic Primary hyperoxaluria, type I 2014-11-27 no assertion criteria provided research

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