ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.691T>C (p.Ser231Pro) (rs5030845)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000190611 SCV000245645 pathogenic Phenylketonuria 2014-09-24 criteria provided, single submitter clinical testing The p.Ser231Pro variant has been reported at least seven individuals with phenylketonuria (PKU) in the homozygous or compound heterozygous state (Effat 1999, Daniele 2008, Hamzelhoei 2012, Ajami 2013), and was not identified in large population studies. In vitro functional assays suggest complete loss of enzymatic activity (Dianzani 1995). In summary, this variant meets our criteria to be classified as pathogenic for PKU in an autosomal recessive manner for PKU based upon presence in affected individuals, absence from controls, and functional evidence (
Counsyl RCV000190611 SCV000796824 pathogenic Phenylketonuria 2018-01-03 criteria provided, single submitter clinical testing
Invitae RCV000190611 SCV001223743 pathogenic Phenylketonuria 2019-05-02 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 231 of the PAH protein (p.Ser231Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another PAH variant in individuals affected with phenylketonuria or hyperphenylalaninemia (PMID: 27682710, 18346471). ClinVar contains an entry for this variant (Variation ID: 102786). This variant has been reported to affect PAH protein function (PMID: 8535444, 10394930). For these reasons, this variant has been classified as Pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089037 SCV000119642 not provided not provided no assertion provided not provided

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