ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.32T>A (p.Leu11Ter) (rs1346707834)

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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 RCV000850222 SCV001370802 pathogenic Phenylketonuria 2020-04-09 reviewed by expert panel curation The p.L11* variant in PAH is a null variant (nonsense 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 one Ugyur proband (PMID: 31355225) with classic 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.R413P variant (known pathogenic per PAH ClinGen working group) (PM3). It is also reported in ClinVar (ID 625287) as a de novo variant by one lab, in a case with PKU; no further information is given.
The Molecular Genetic Diagnosis Center, Children’s Hospital of Fudan University RCV000850222 SCV000893128 pathogenic Phenylketonuria 2019-03-08 no assertion criteria provided clinical testing

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