ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1099del (p.Leu367fs) (rs62506951)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781680 SCV000919922 likely pathogenic Phenylketonuria 2018-08-27 criteria provided, single submitter clinical testing Variant summary: PAH c.1099delC (p.Leu367TrpfsX33) 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 allele was found at a frequency of 4.1e-06 in 245994 control chromosomes. c.1099delC has been reported in the literature in individuals affected with Phenylalanine Hydroxylase Deficiency (Phenylketonuria). These data indicate that the variant may be associated with disease. 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.
Invitae RCV000781680 SCV001199465 pathogenic Phenylketonuria 2019-12-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu367Trpfs*33) in the PAH 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 in individual(s) with phenylketonuria (PMID: 29176022, 29499199). ClinVar contains an entry for this variant (Variation ID: 102524). Loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518). For these reasons, this variant has been classified as Pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088757 SCV000119341 not provided not provided no assertion provided not provided

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