ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.656T>A (p.Phe219Tyr)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002364449 SCV002665976 uncertain significance Inborn genetic diseases 2022-04-05 criteria provided, single submitter clinical testing The p.F219Y variant (also known as c.656T>A), located in coding exon 6 of the PAH gene, results from a T to A substitution at nucleotide position 656. The phenylalanine at codon 219 is replaced by tyrosine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003098292 SCV003281776 uncertain significance Phenylketonuria 2022-02-06 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 219 of the PAH protein (p.Phe219Tyr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PAH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

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