ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.189_190dup (p.His64fs)

dbSNP: rs672601294
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000993630 SCV001146762 pathogenic Phenylketonuria 2019-04-04 reviewed by expert panel curation The c.189_190dupTGAC variant in PAH has been previously reported as a single heterozygous variant in a 2.5 year old Chinese proband with PKU, with a second mutation not detected; exact plasma Phe levels were not given, but said to be >20mg/dL and BH4 deficiency was formally excluded by urinary pterin analysis and blood neopterin dihydropteridine reductase assays (PMID: 23271928; PMID: 25863075) (PP4_Moderate). The variant is a frameshift variant which occurs in exon 3 of 13 in the in the canonical transcript of PAH, a gene fulfilling the most recent criteria for LOF being a known disease mechanism (see PMID: 30192042) (PVS1). It is absent from control databases including ethnically matched individuals, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4_Moderate.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.