Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000850225 | SCV001370800 | likely pathogenic | Phenylketonuria | 2020-03-26 | reviewed by expert panel | curation | The c.1109A>G (p.Glu370Gly) variant in PAH has been reported in a Uygur patient with moderate PKU (BH4 deficiency ruled out) (PP4_Moderate; PMID: 31355225). This variant was detected with p.Val230Ile (Likely pathogenic in ClinVar) (PM3; PMID: 31355225). The variant is absent from population databases (PM2). Computational evidence is conflicting. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP4_Moderate. |
Baylor Genetics | RCV000850225 | SCV004209607 | likely pathogenic | Phenylketonuria | 2023-08-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000850225 | SCV004537104 | likely pathogenic | Phenylketonuria | 2023-07-31 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 not expected to disrupt PAH protein function. ClinVar contains an entry for this variant (Variation ID: 625290). This missense change has been observed in individual(s) with hyperphenylalaninemia (PMID: 31355225). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 370 of the PAH protein (p.Glu370Gly). |
Center for Molecular Medicine, |
RCV000850225 | SCV000893131 | pathogenic | Phenylketonuria | 2019-03-08 | no assertion criteria provided | clinical testing |