Submissions for variant NM_000277.3(PAH):c.716G>A (p.Gly239Asp)

dbSNP: rs62507283

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001857432	SCV002243742	pathogenic	Phenylketonuria	2021-03-22	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly239 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10394930, 31208052, 7833954, 9391881). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has been observed in individual(s) with hyperphenylalaninemia (PMID: 16256386, 30050108). ClinVar contains an entry for this variant (Variation ID: 102798). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 239 of the PAH protein (p.Gly239Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000089049	SCV000119654	not provided	not provided		no assertion provided	not provided