Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000169464 | SCV001370877 | pathogenic | Phenylketonuria | 2020-05-31 | reviewed by expert panel | curation | The c.694C>T (p.Gln232Ter) variant in PAH has been reported in multiple individuals with PKU (PP4; PMID: 30050108). This variant has an extremely low allele frequency (MAF=0.00003; PM2). This variant was detected with known pathogenic variant c.442-1G>A (PM3; PMID: 30050108). This is a null variant (nonsense) in exon 6 of 13 (NMD predicted) of PAH, a gene where loss of function is a known mechanism of disease (PVS1). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, PP4. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000089039 | SCV000601715 | pathogenic | not provided | 2017-05-19 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000169464 | SCV001386850 | pathogenic | Phenylketonuria | 2023-11-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln232*) 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). This variant is present in population databases (rs62507348, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with PAH-related conditions (PMID: 16256386, 23932990, 25087612, 26600521, 27264808, 29390883). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 102788). For these reasons, this variant has been classified as Pathogenic. |
De |
RCV000089039 | SCV000119644 | not provided | not provided | no assertion provided | not provided | ||
Counsyl | RCV000169464 | SCV000220898 | pathogenic | Phenylketonuria | 2019-06-10 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000169464 | SCV002088648 | pathogenic | Phenylketonuria | 2020-09-11 | no assertion criteria provided | clinical testing |