Submissions for variant NM_000277.3(PAH):c.400C>T (p.Gln134Ter)

dbSNP: rs199475680

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV000169559	SCV002818516	pathogenic	Phenylketonuria	2022-10-14	reviewed by expert panel	curation	This c.400C>T (p.Gln134Ter) variant in PAH was detected in a patient with PKU (PMID:17096675). This variant was absent in population databases. This was predicted as a null variant in PAH where LOF is a known mechanism of disease. This is a nonsense variant in exon 4 of 13 coding exons predicted to undergo nonsense mediated decay. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1,PM2,PP4.
Counsyl	RCV000169559	SCV000221054	likely pathogenic	Phenylketonuria	2015-01-21	criteria provided, single submitter	literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000169559	SCV000919915	pathogenic	Phenylketonuria	2024-10-15	criteria provided, single submitter	clinical testing	Variant summary: PAH c.400C>T (p.Gln134X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 251466 control chromosomes. c.400C>T has been reported in the literature in at least 1 individual affected with Phenylalanine Hydroxylase Deficiency (Phenylketonuria) (example, Hillert_2020). The following publication has been ascertained in the context of this evaluation (PMID: 32668217). ClinVar contains an entry for this variant (Variation ID: 102664). Based on the evidence outlined above, the variant was classified as pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088912	SCV000119510	not provided	not provided		no assertion provided	not provided