ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.491T>C (p.Ile164Thr)

dbSNP: rs199475595
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002514543 SCV003441158 pathogenic Phenylketonuria 2022-10-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ile164 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11244681, 23942198, 27121329; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PAH protein function. ClinVar contains an entry for this variant (Variation ID: 102699). This missense change has been observed in individual(s) with hyperphenylalaninemia (PMID: 17502162, 32668217; BIOPKU http://www.biopku.org). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 164 of the PAH protein (p.Ile164Thr).
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088947 SCV000119548 not provided not provided no assertion provided not provided

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