Submissions for variant NM_000277.3(PAH):c.227A>C (p.Glu76Ala)

dbSNP: rs62507347

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001389298	SCV001590609	pathogenic	Phenylketonuria	2020-07-30	criteria provided, single submitter	clinical testing	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. This variant disrupts the p.Glu76 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12655546, 24401910, 11935335). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has been observed in individual(s) with PAH-related conditions (PMID: 8632937, Invitae). ClinVar contains an entry for this variant (Variation ID: 102634). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with alanine at codon 76 of the PAH protein (p.Glu76Ala). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and alanine.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088877	SCV000119474	not provided	not provided		no assertion provided	not provided