Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000000611 | SCV000852165 | pathogenic | Phenylketonuria | 2018-08-10 | reviewed by expert panel | curation | PAH-specific ACMG/AMP criteria applied: PVS1: Nonsense variant; PP4_Moderate: Seen in multiple Chinese PKU patients. BH4 deficiency excluded. (PMID:1301187; PMID:2816939; PMID:9860305); PM3: Detected with R243Q, pathogenic in ClinVar (PMID:15503242). In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PVS1, PP4_Moderate, PM3). |
Eurofins Ntd Llc |
RCV000088898 | SCV000228838 | pathogenic | not provided | 2015-02-18 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000000611 | SCV000629190 | pathogenic | Phenylketonuria | 2025-01-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg111*) 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 (rs76296470, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with phenylketonuria (PMID: 12542580, 16256386, 21307867, 24401910, 27121329). ClinVar contains an entry for this variant (Variation ID: 581). For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV000000611 | SCV000893952 | pathogenic | Phenylketonuria | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000000611 | SCV000919917 | pathogenic | Phenylketonuria | 2018-08-03 | criteria provided, single submitter | clinical testing | Variant summary: PAH c.331C>T (p.Arg111X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.2e-05 in 246200 control chromosomes (gnomAD). The variant, c.331C>T, has been reported in the literature in multiple individuals affected with Phenylalanine Hydroxylase Deficiency (Phenylketonuria)(Tao_2015, Tyfield_1995). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cites the variant as "pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic. |
Revvity Omics, |
RCV000000611 | SCV002016473 | pathogenic | Phenylketonuria | 2020-11-20 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000000611 | SCV004201372 | pathogenic | Phenylketonuria | 2024-03-26 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000088898 | SCV005414123 | pathogenic | not provided | 2023-08-07 | criteria provided, single submitter | clinical testing | PM2_moderate, PVS1 |
Juno Genomics, |
RCV000000611 | SCV005415688 | pathogenic | Phenylketonuria | criteria provided, single submitter | clinical testing | PM2_Supporting+PVS1+PM3_VeryStrong | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000088898 | SCV005624691 | pathogenic | not provided | 2024-07-12 | criteria provided, single submitter | clinical testing | The PAH c.331C>T (p.Arg111*) variant (also known as R111X) causes the premature termination of PAH protein synthesis. In the published literature, this variant has been reported in many individuals affected with phenylketonuria (PKU) (PMIDs: 17935162 (2008), 24401910 (2014), 29288420 (2018), 29413232 (2018), 36104584 (2022), and Gundorova et al. 2019 Russ J Genet 55:1025). The frequency of this variant in the general population, 0.000035 (4/113714 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. |
OMIM | RCV000000611 | SCV000020761 | pathogenic | Phenylketonuria | 1990-05-01 | no assertion criteria provided | literature only | |
De |
RCV000088898 | SCV000119496 | not provided | not provided | no assertion provided | not provided | ||
Counsyl | RCV000000611 | SCV000485304 | pathogenic | Phenylketonuria | 2016-01-21 | no assertion criteria provided | clinical testing | |
Natera, |
RCV000000611 | SCV001455111 | pathogenic | Phenylketonuria | 2020-09-16 | no assertion criteria provided | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000088898 | SCV001931381 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000088898 | SCV001959189 | pathogenic | not provided | no assertion criteria provided | clinical testing |