ClinVar Miner

Submissions for variant NM_000277.1(PAH):c.913_1199del (p.Ile306Leufs)

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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 RCV000000669 SCV001146698 pathogenic Phenylketonuria 2019-07-14 reviewed by expert panel curation The c.913_1199del (p.Ile306Leufs) variant in PAH has been previously reported in a proband with mild PKU; BH4 deficiency does not appear to have been excluded (PP4). It was found in trans (confirmed via paternal testing) with the known Pathogenic variant p.Glu390Gly (see ClinVar ID 625, PM3). The sequence change results a deletion involving exons 9, 10 and 11 leading to a frameshift variant in the in the canonical transcript of PAH, a gene fulfilling the most recent criteria for LOF being a known disease mechanism (see PMID: 30192042) (PVS1). It is absent from control databases (PM2). ). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, PP4.
OMIM RCV000000669 SCV000020819 pathogenic Phenylketonuria 1999-08-01 no assertion criteria provided literature only

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