ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.770G>T (p.Gly257Val) (rs62642908)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668413 SCV000793007 likely pathogenic Phenylketonuria 2017-07-25 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000668413 SCV000919916 pathogenic Phenylketonuria 2018-08-02 criteria provided, single submitter clinical testing Variant summary: PAH c.770G>T (p.Gly257Val) results in a non-conservative amino acid change located in the Aromatic amino acid hydroxylase, C-terminal domain (IPR019774) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246102 control chromosomes (in gnomAD). c.770G>T has been reported in the literature in multiple individuals affected with Phenylalanine Hydroxylase Deficiency (Phenylketonuria) (e.g. Liang 2014, Li 2015, Liu 2017). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Liang 2014). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089087 SCV000119693 not provided not provided no assertion provided not provided

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