ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.775G>A (p.Ala259Thr) (rs62642932)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411173 SCV000485962 likely pathogenic Phenylketonuria 2016-03-08 criteria provided, single submitter clinical testing
Invitae RCV000411173 SCV001381833 pathogenic Phenylketonuria 2019-09-09 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 259 of the PAH protein (p.Ala259Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs62642932, ExAC 0.01%). This variant has been observed in combination with another PAH variant in many individuals affected with classic phenylketonuria (PMID: 8831077, 18985011, 11142755, 23932990, 15503242). ClinVar contains an entry for this variant (Variation ID: 102831). This variant has been reported to affect PAH protein function (PMID: 21953985, 9799096, 17924342, 10980574). This variant disrupts the p.Ala259 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 26666653, 18299955, 2035532). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089088 SCV000119694 not provided not provided no assertion provided not provided

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