Submissions for variant NM_000277.3(PAH):c.305T>C (p.Ile102Thr)

dbSNP: rs62508591

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome-Nilou Lab	RCV001580454	SCV001810538	likely pathogenic	Phenylketonuria	2021-07-22	criteria provided, single submitter	clinical testing
Invitae	RCV001580454	SCV003441162	pathogenic	Phenylketonuria	2022-08-31	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 102 of the PAH protein (p.Ile102Thr). This missense change has been observed in individual(s) with hyperphenylalaninemia (PMID: 30389586, 32668217). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PAH protein function. ClinVar contains an entry for this variant (Variation ID: 102648).
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088894	SCV000119492	not provided	not provided		no assertion provided	not provided