ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.649T>C (p.Cys217Arg)

dbSNP: rs62508718
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000664975 SCV003441222 likely pathogenic Phenylketonuria 2022-01-16 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Cys217 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8807319, 32668217). 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 expected to disrupt PAH protein function. ClinVar contains an entry for this variant (Variation ID: 102770). This missense change has been observed in individual(s) with clinical features of hyperphenylalaninemia (PMID: 18798839, 29499199, 32668217). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 217 of the PAH protein (p.Cys217Arg).
Baylor Genetics RCV000664975 SCV005053841 likely pathogenic Phenylketonuria 2023-12-24 criteria provided, single submitter clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089020 SCV000119625 not provided not provided no assertion provided not provided
Counsyl RCV000664975 SCV000789021 uncertain significance Phenylketonuria 2016-12-27 flagged submission clinical testing

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