Submissions for variant NM_000277.3(PAH):c.591G>C (p.Leu197Phe)

dbSNP: rs281865442

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV000106361	SCV001146740	likely pathogenic	Phenylketonuria	2019-05-04	reviewed by expert panel	curation	The c.591G>C (p.Leu197Phe) variant in PAH has been reported in 3 individuals with classic PKU (BH4 deficiency excluded). (PP4_Moderate; PMID: 18299955). This variant is absent in population databases (PM2). This variant was detected with a pathogenic variant (c.168+1G>A) and twice in the homozygous state (PM3). Multiple lines of computational evidence support a deleterious effect (SIFT, PolyPhen2, MutationTaster, REVEL=0.82). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3, PP3.
Baylor Genetics	RCV000106361	SCV004209715	pathogenic	Phenylketonuria	2023-01-01	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000106361	SCV004805057	pathogenic	Phenylketonuria	2024-03-17	criteria provided, single submitter	research
Inserm U 954, Faculté de Médecine de Nancy	RCV000106361	SCV000143861	probable-pathogenic	Phenylketonuria		no assertion criteria provided	not provided	Converted during submission to Likely pathogenic.