Please note this is a beta version of the ClinGen Evidence Repository. This resource is intended to provide access to variant level evidence used and applied by ClinGen Variant Curation Expert Panels in the classification of variants. In this beta version, the evidence is limited to curation notes and referenced literature (PMIDs).
For general information about ClinGen Expert Panels and Variant Curation please visit: Clinical Domain Working Groups. For specific inquiries regarding a variant classification or evidence curation (e.g. population database queried, segregation counts or other evidence used) or to submit general comments about the evidence repo, please email us.
The resource is undergoing updates and tesing. Should you encounter any issues regarding the data displayed, lack of functionality or other problems, please let us know so we can rectify these accordingly. Your help in this regard is greatly appreciated.
PAH-specific ACMG/AMP criteria applied: PM2: gnomAD MAF=0.00002; PP4_Moderate: Seen in PKU patients. BH4 disorders ruled out. (PMID:2574002); PS3: <3% (PMID:9450897). PM3: Detected in trans with known pathogenic variants. In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PM3, PP4_Moderate, PS3). Updated to reflect new PVS1 recommendations.
Met criteria codes
Detected in trans with c.1315+1G>A (known pathogenic), and also in the homozygous state.
A proband was homozygous for this mutation (A-to-G transition (met-val) in codon1]. In other probands, the codon1 mutation was inherited once with the splice junction mutation in exon 12 (c.1315+1G>A),and was inherited twice with a mutation on haplotype 1.
Seen in PKU patients. BH4 disorders ruled out.
Analysis of RFLP haplotypes and mutations revealed a novel mutation, an A-to-G transition (met----val) in codon 1 (the translation-initiation codon). It occurred on 5 of the 18 mutant chromosomes. A proband homozygous for this mutation had the PKU phenotype. The appropriate biochemical tests were done to rule out disorders of tetrahydrobiopterin homeostasis.
< 3 PAH enzyme activity as % of wild type. (p91023(B)/COS
Unmet criteria codes
Initiation codon variant
Approved on: 2019-03-23
Published on: 2019-05-10
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. If you have questions about the information contained on this website, please see a health care professional.