ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1216A>G (p.Ile406Val) (rs749613899)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel, RCV000758135 SCV000886621 likely pathogenic Phenylketonuria 2018-12-09 reviewed by expert panel curation The c.1216A>G (p.Ile406Val) variant in PAH is reported in an individual with PKU. Dihydropteridine reductase activity, urinary biopterin and neopterin ratio, and tetrahydrobiopterin loading were collected. (PMID: 26503515) This variant has a low frequency in ExAC/gnomAD (MAF=0.00016) and is absent from 1000G. A deleterious effect is predicted by SIFT, Polyphen, and MutationTaster. Another missense variant at this amino acid is interpreted as likely pathogenic by our PAH VCEP (p.I406T). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP4_Moderate, PP3.

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