ClinVar Miner

Submissions for variant NM_000317.3(PTS):c.166G>A (p.Val56Met) (rs104894277)

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
Counsyl RCV000000510 SCV000791881 likely pathogenic BH4-deficient hyperphenylalaninemia A 2017-05-30 criteria provided, single submitter clinical testing
Invitae RCV000000510 SCV000957583 pathogenic BH4-deficient hyperphenylalaninemia A 2019-10-11 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 56 of the PTS protein (p.Val56Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs104894277, ExAC 0.02%). This variant has been observed in combination with another PTS variant in multiple individuals affected with biopterin deficient hyperphenylalanemia (PMID: 9450907, 23138986). ClinVar contains an entry for this variant (Variation ID: 481). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000510 SCV000020659 pathogenic BH4-deficient hyperphenylalaninemia A 1998-01-01 no assertion criteria provided literature only
Natera, Inc. RCV001271443 SCV001452592 pathogenic 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency 2020-09-16 no assertion criteria provided clinical testing

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.