Submissions for variant NM_000277.3(PAH):c.181A>G (p.Asn61Asp)

dbSNP: rs199475651

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001389299	SCV001590610	pathogenic	Phenylketonuria	2020-04-12	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Asn61 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10234516). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant has been observed in combination with another PAH variant in individual(s) affected with mild phenylketonuria (PMID: 12501224, Invitae). ClinVar contains an entry for this variant (Variation ID: 102617). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with aspartic acid at codon 61 of the PAH protein (p.Asn61Asp). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and aspartic acid.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088859	SCV000119454	not provided	not provided		no assertion provided	not provided