ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.590T>A (p.Leu197Ter) (rs886042078)

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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 RCV000850223 SCV001370803 pathogenic Phenylketonuria 2020-04-16 reviewed by expert panel curation The c.590T>A (p.Leu197Ter) 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 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.R53H variant (VUS per ClinGen PAH working group) (0.25 points per SVI criteria for PM3, and thus insufficient to use PM3 at any strength). It is also reported pathogenic in Clinvar (ID 625288) 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 RCV000850223 SCV000893129 pathogenic Phenylketonuria 2019-03-08 no assertion criteria provided clinical testing

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