Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV001269070 | SCV001448294 | likely pathogenic | Phenylketonuria | 2020-10-15 | reviewed by expert panel | curation | The c.1199+4A>G PAH variant has been reported in 1 Danish patient with classic phenylketonuria (PMID: 26542770) detected with the pathogenic PAH variant c.1315+1G>A. A defect in BH4 metabolism was not excluded. This variant is absent from population databases. It is intronic and multiple lines of computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP3, PP4. |
| Labcorp Genetics |
RCV001269070 | SCV004294255 | likely pathogenic | Phenylketonuria | 2023-07-24 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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: 987771). This variant has been observed in individual(s) with hyperphenylalaninemia (PMID: 26542770, 32668217). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 11 of the PAH gene. It does not directly change the encoded amino acid sequence of the PAH protein. It affects a nucleotide within the consensus splice site. |