Submissions for variant NM_000277.3(PAH):c.506G>C (p.Arg169Pro)

dbSNP: rs199475679

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV000515792	SCV001572876	uncertain significance	Phenylketonuria	2021-03-26	reviewed by expert panel	curation	The c.506G>C (p.Arg169Pro) variant in PAH is reported as Likely Pathogenic by one clinical laboratory in ClinVar (see variant ID 446524); no further information is provided. At the time of review, the variant does not appear to be reported in the published literature and/or in the BioPKU database. The variant is predicted damaging by multiple lines of computational evidence (PP3). It is absent in gnomAD (PM2). Other missense variants at this site are pathogenic/likely pathogenic – p.Arg169Ser (variant ID 932262), p.Arg169His (variant ID 102706), p.Arg169Gly (variant ID 551103), and p.Arg169Cys (variant ID 125436) (PM5). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3.
Medical Genetics Center, Academic Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi	RCV000515792	SCV000611630	likely pathogenic	Phenylketonuria	2017-10-18	no assertion criteria provided	clinical testing	The mutation has been detected in compound heterozygous state with another pathogenic mutation (c.506G>C) in a 5 years old girl affected with PKU and was found in heterozygous in her father.