ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.71A>G (p.Tyr24Cys)

gnomAD frequency: 0.00003  dbSNP: rs539994406
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000529284 SCV000629208 uncertain significance Phenylketonuria 2022-01-26 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 24 of the PAH protein (p.Tyr24Cys). This variant is present in population databases (rs539994406, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with PAH-related conditions. ClinVar contains an entry for this variant (Variation ID: 458080). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Laboratory Services, Illumina RCV000529284 SCV001266461 uncertain significance Phenylketonuria 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Natera, Inc. RCV000529284 SCV002088680 uncertain significance Phenylketonuria 2019-10-28 no assertion criteria provided clinical testing

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