ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.940C>A (p.Pro314Thr) (rs199475650)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672630 SCV000797754 likely pathogenic Phenylketonuria 2018-02-08 criteria provided, single submitter clinical testing
Invitae RCV000672630 SCV000962218 pathogenic Phenylketonuria 2019-10-09 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 314 of the PAH protein (p.Pro314Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. 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 hyperphenylalaninemia (PMID: 28982351, 24401910, 29390883). ClinVar contains an entry for this variant (Variation ID: 102904). Experimental studies have shown that this missense change does not disrupt PAH activity in vitro (PMID: 18590700). This variant disrupts the p.Pro314 amino acid residue in PAH. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 8807319, 12501224), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089168 SCV000119783 not provided not provided no assertion provided not provided

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