ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.620A>G (p.Asn207Ser) (rs62508721)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668775 SCV000793428 uncertain significance Phenylketonuria 2017-08-22 criteria provided, single submitter clinical testing
Invitae RCV000668775 SCV001213212 likely pathogenic Phenylketonuria 2019-12-03 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 207 of the PAH protein (p.Asn207Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with hyperphenylalaninemia (PMID: 9048935, 17096675). ClinVar contains an entry for this variant (Variation ID: 102765). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Asn207 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9452061, 12554741). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089015 SCV000119619 not provided not provided no assertion provided not provided

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.