ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1171A>G (p.Ser391Gly)

dbSNP: rs281865453
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000106342 SCV001370817 uncertain significance Phenylketonuria 2020-04-10 reviewed by expert panel curation The c.1171A>G (p.Ser391Gly) variant in PAH has been reported in at least 1 individual with classic PKU (PMID: 26666653). However, the patient genotype included pathogenic variants c.194 T>C; p.Ile65Thr (ClinVar: 636), c.1169A>G; p.Glu390Gly (ClinVar: 625), and this variant c.1171A>G (p.Ser391Gly) with phasing not confirmed. This variant was absent in population databases (PM2). Computational prediction tools suggest that the c.1171A>G variant may impact the protein (PP3). The alternate missense changes of Ser391Ile (interpreted as Pathogenic by the ClinGen PAH Expert Panel) and Ser391Thr (ClinVar 225136, Likely Pathogenic) have been reported at the same amino acid residue (PM5). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3.
Inserm U 954, Faculté de Médecine de Nancy RCV000106342 SCV000143841 probable-pathogenic Phenylketonuria no assertion criteria provided not provided Converted during submission to Likely 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.