Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000410471 | SCV000487095 | likely pathogenic | Phenylketonuria | 2016-10-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000410471 | SCV000827177 | pathogenic | Phenylketonuria | 2023-07-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PAH protein in which other variant(s) (p.Ala447Asp) have been determined to be pathogenic (PMID: 8659548, 9540801, 23430918). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This sequence change creates a premature translational stop signal (p.Gln428*) in the PAH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 25 amino acid(s) of the PAH protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hyperphenylalaninemia (PMID: 34828281). ClinVar contains an entry for this variant (Variation ID: 371497). |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759177 | SCV000888343 | likely pathogenic | not provided | 2018-04-26 | criteria provided, single submitter | clinical testing |