Submissions for variant NM_000277.3(PAH):c.992T>G (p.Phe331Cys)

dbSNP: rs199475614

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002515785	SCV003441153	pathogenic	Phenylketonuria	2022-10-08	criteria provided, single submitter	clinical testing	This variant disrupts the p.Phe331 amino acid residue in PAH. Other variant(s) that disrupt this residue have been observed in individuals with PAH-related conditions (PMID: 7833954, 23764561), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 331 of the PAH protein (p.Phe331Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hyperphenylalaninemia (PMID: 8659548; Invitae). ClinVar contains an entry for this variant (Variation ID: 102926). 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.
Baylor Genetics	RCV002515785	SCV004201980	likely pathogenic	Phenylketonuria	2022-05-18	criteria provided, single submitter	clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000089193	SCV000119809	not provided	not provided		no assertion provided	not provided