ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1147C>T (p.Gln383Ter)

dbSNP: rs1037293795
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
ClinGen PAH Variant Curation Expert Panel RCV000409716 SCV000886609 pathogenic Phenylketonuria 2018-12-09 reviewed by expert panel curation The c.1147C>T (p.Gln383Ter) variant in PAH is a nonsense variant predicted to undergo NMD, present in all biologically relevant transcripts, absent from all populations databases. It has been identified in a patient with classic PKU as homozygous, and in trans with a pathogenic variant (R408W), although defect in BH4 metabolism was not excluded in either patient. (PMID: 24350308, 22763404). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, PP4.
Counsyl RCV000409716 SCV000486081 likely pathogenic Phenylketonuria 2016-03-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000409716 SCV003441002 pathogenic Phenylketonuria 2022-07-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 370701). This premature translational stop signal has been observed in individual(s) with hyperphenylalaninemia and/or phenylketonuria (PMID: 22763404, 24350308, 29499199, 32668217). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln383*) in the PAH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518).

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.