ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.581T>C (p.Leu194Pro) (rs5030844)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel, RCV000411842 SCV000852161 likely pathogenic Phenylketonuria 2018-08-13 reviewed by expert panel curation PAH-specific ACMG/AMP criteria applied: PM2: Absent from 1000G, ESP. gnomAD MAF:0.00004.; PP3: Predicted deleterious in SIFT, Polyphen-2, MutationTaster. REVEL=0.899; PM3_Strong: Detected in trans with V245A and R261X, both pathogenic (PMID:7981714; PMID:16601866); PP4_Moderate: Detected in 3 patients (1 HPA, 1 PKU). BH4 deficiency excluded in 2 patients. (PMID:8533759; PMID:7981714; PMID:9012412; PMID:16601866). In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PP3, PM3_Strong, PP4_Moderate).
Counsyl RCV000411842 SCV000486100 likely pathogenic Phenylketonuria 2016-03-29 criteria provided, single submitter clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088991 SCV000119595 not provided not provided no assertion provided not provided
GeneDx RCV000088991 SCV000582140 pathogenic not provided 2018-08-10 criteria provided, single submitter clinical testing The L194P variant has also been previously reported inindividuals with PKU (Zschocke et al., 1995; Tyfield et al., 1997; Utz et al., 2012; Ho et al., 2014;Manti et al., 2016). It is unknown if this variant is responsive to BH4 therapy (Jeannesson-Thivisol etal., 2015).

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