ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1218A>G (p.Ile406Met) (rs773526027)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel, RCV000668256 SCV000886605 likely pathogenic Phenylketonuria 2018-12-09 reviewed by expert panel curation The c.1218A>G (p.Ile406Met) variant in PAH is reported in 2 individuals with non-PKU HPA. BH4 assessment was not stated. It was detected with a known pathogenic variant, p.Arg408Trp. (PMID: 23357515) This variant has a low allele frequency in gnomAD and ExAC (MAF=0.00003) and is absent in 1000G. Computational evidence is discordant. Another missense change at this amino acid is interpreted as likely pathogenic by the 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, PM3, PM5, PP4.
Counsyl RCV000668256 SCV000792829 uncertain significance Phenylketonuria 2017-07-17 criteria provided, single submitter clinical testing

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