Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000409716 | SCV000886609 | pathogenic | Phenylketonuria | 2018-12-09 | reviewed by expert panel | curation | The c.1147C>T (p.Gln383Ter) variant in PAH is a nonsense variant predicted to undergo NMD, present in all biologically relevant transcripts, absent from all populations databases. It has been identified in a patient with classic PKU as homozygous, and in trans with a pathogenic variant (R408W), although defect in BH4 metabolism was not excluded in either patient. (PMID: 24350308, 22763404). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, PP4. |
Counsyl | RCV000409716 | SCV000486081 | likely pathogenic | Phenylketonuria | 2016-03-24 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000409716 | SCV003441002 | pathogenic | Phenylketonuria | 2022-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 370701). This premature translational stop signal has been observed in individual(s) with hyperphenylalaninemia and/or phenylketonuria (PMID: 22763404, 24350308, 29499199, 32668217). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln383*) in the PAH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518). |