Submissions for variant NM_000277.3(PAH):c.1054G>T (p.Gly352Cys)

dbSNP: rs62508686

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002514541	SCV003441004	pathogenic	Phenylketonuria	2023-10-08	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 352 of the PAH protein (p.Gly352Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PAH-related conditions (PMID: 16601866, 32668217). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 102497). 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. For these reasons, this variant has been classified as Pathogenic.
Intergen, Intergen Genetics and Rare Diseases Diagnosis Center	RCV002514541	SCV004035223	likely pathogenic	Phenylketonuria	2023-09-19	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV002514541	SCV004201981	likely pathogenic	Phenylketonuria	2022-05-03	criteria provided, single submitter	clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088728	SCV000119310	not provided	not provided		no assertion provided	not provided