Submissions for variant NM_000277.3(PAH):c.1024G>A (p.Ala342Thr)

dbSNP: rs62507282

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001386152	SCV001586284	pathogenic	Phenylketonuria	2024-06-10	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 342 of the PAH protein (p.Ala342Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with phenylketonuria (PMID: 23932990, 30050108, 32668217; BIOPKU http://www.biopku.org). ClinVar contains an entry for this variant (Variation ID: 102473). 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 with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PAH function (PMID: 17924342). For these reasons, this variant has been classified as Pathogenic.
New York Genome Center	RCV001386152	SCV001622886	likely pathogenic	Phenylketonuria	2020-05-07	criteria provided, single submitter	clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088704	SCV000119284	not provided	not provided		no assertion provided	not provided