ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.601C>T (p.His201Tyr) (rs62517205)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089001 SCV000119605 not provided not provided no assertion provided not provided
GenomeConnect, ClinGen RCV000509208 SCV000607300 not provided Phenylketonuria no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Integrated Genetics/Laboratory Corporation of America RCV000588479 SCV000696446 pathogenic Hyperphenylalaninemia, non-pku 2017-04-13 criteria provided, single submitter clinical testing Variant summary: The PAH c.601C>T (p.His201Tyr) variant located in the Aromatic amino acid hydroxylase, C-terminal (via InterPro) involves the alteration of a conserved nucleotide and 3/5 in silico tools predict a damaging outcome. Reblova_2013 indicates that the His201 plays a key role in forming a H-bond needed for stablization. This variant is absent in 121300 control chromosomes (ExAC). Multiple publications have cited the variant in affected compound heterozygote individuals, predominantly from Italy, with a mild HPA. Taken together, the variant of interest has been classified as "pathogenic."
Invitae RCV000509208 SCV000629203 pathogenic Phenylketonuria 2018-09-25 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 201 of the PAH protein (p.His201Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals diagnosed with hyperphenylalaninemia co-occurring with known pathogenic PAH variants (PMID: 9521426, 10598814, 16198137, 23792259). ClinVar contains an entry for this variant (Variation ID: 102752). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.

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.