ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.526C>T (p.Arg176Ter) (rs199475575)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000179282 SCV000852175 pathogenic Phenylketonuria 2018-08-13 reviewed by expert panel curation PAH-specific ACMG/AMP criteria applied: PVS1: Nonsense variant; PM2: ExAC MAF: 0.00010; PP4_Moderate: BH4 defect excluded in all patients in Liu 2015. Identified in 6 patients in this study (PMID:10394930; PMID:26600521); PM3_Strong: Identified in 6 patients, in trans with R243Q and R241C (both pathogenic) (PMID:26600521). 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: (PVS1, PM2, PP4_Moderate, PM3_Strong).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000088971 SCV000231507 pathogenic not provided 2014-08-08 criteria provided, single submitter clinical testing
Invitae RCV000179282 SCV000629197 pathogenic Phenylketonuria 2019-09-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 176 (p.Arg176*) of 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. This particular variant has been reported in several individuals affected with phenyketonuria and is associated with the classical form of the disease in the homozygous state (PMID: 8268925, 17935162, 23514811, 26413448, 26503515). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000179282 SCV000696453 pathogenic Phenylketonuria 2016-03-03 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000179282 SCV000744099 pathogenic Phenylketonuria 2014-10-08 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000179282 SCV000745573 pathogenic Phenylketonuria 2016-07-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000088971 SCV000888349 pathogenic not provided 2018-07-20 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000179282 SCV000893951 pathogenic Phenylketonuria 2018-10-31 criteria provided, single submitter clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088971 SCV000119574 not provided not provided no assertion provided not provided
Counsyl RCV000179282 SCV000485295 pathogenic Phenylketonuria 2016-01-21 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.