ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1069T>C (p.Cys357Arg)

dbSNP: rs62508595
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667720 SCV000792215 uncertain significance Phenylketonuria 2017-06-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000667720 SCV004294269 pathogenic Phenylketonuria 2023-06-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys357 amino acid residue in PAH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32668217; BIOPKU http://www.biopku.org). 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: 552458). This missense change has been observed in individual(s) with hyperphenylalaninemia (PKU) (PMID: 26413448, 32668217; BIOPKU http://www.biopku.org). 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 357 of the PAH protein (p.Cys357Arg).

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