ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.346_347del (p.Asp116fs) (rs1592978629)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000851537 SCV001370820 pathogenic Phenylketonuria 2020-04-16 reviewed by expert panel curation The c.346_347del (p.Asp116fs) variant in PAH is a null variant (frameshift variant) in a gene where LOF is a known mechanism of disease, leading to premature truncation and NMD (PVS1). It is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). It has been previously reported in an Ugyur proband (PMID: 31355225) with mild PKU; BH4 deficiency was formally excluded by urinary pterin analysis (PP4_Moderate). The patient was compound heterozygous for the variant (confirmed by parental testing) and carried it in trans with the p.E390G variant (Likely Pathogenic per ClinGen PAH working group) (PM3). It is also reported pathogenic in Clinvar (ID 635217) by one lab, in a case with PKU; no further information is given.
The Molecular Genetic Diagnosis Center, Children’s Hospital of Fudan University RCV000851537 SCV000924699 pathogenic Phenylketonuria 2019-03-08 no assertion criteria provided clinical testing

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