ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.833C>A (p.Thr278Asn) (rs62507262)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665406 SCV000789524 likely pathogenic Phenylketonuria 2017-02-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000665406 SCV001361333 pathogenic Phenylketonuria 2019-10-28 criteria provided, single submitter clinical testing Variant summary: PAH c.833C>A (p.Thr278Asn) results in a non-conservative amino acid change located in the Eukaryotic phenylalanine-4-hydroxylase, catalytic domain (IPR041912) 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 251320 control chromosomes (gnomAD). c.833C>A has been reported in the literature in multiple individuals affected with Phenylalanine Hydroxylase Deficiency (Phenylketonuria) (Guldberg_1993, Fiori_2005, Sarkissian_2011, Polak_2013). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089123 SCV000119731 not provided not provided no assertion provided not provided

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