ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.196G>T (p.Glu66Ter)

dbSNP: rs281865454
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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 RCV000106351 SCV001146718 pathogenic Phenylketonuria 2019-05-26 reviewed by expert panel curation The c.196G>T (p.Glu66Ter) variant in PAH has been previously reported in one proband with classic PKU (PMID: 26666653) (PP4). The proband was heterozygous for the variant and also harbor the pathogenic allele (per ClinGen VCEP) c. 1315+1G>A; however, the phase of the variants was not confirmed via parental testing. (PM3_supporting). The sequence change results in a nonsense variant which occurs in exon 3 of 13 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, PP4, PM3_supporting.
Inserm U 954, Faculté de Médecine de Nancy RCV000106351 SCV000143850 probable-pathogenic Phenylketonuria no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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