ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.283A>T (p.Ile95Phe) (rs62508682)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000088890 SCV000329447 pathogenic not provided 2016-08-11 criteria provided, single submitter clinical testing The I95F variant is also located in the regulatory domain of the phenylalanine hydroxylase enzyme and has previously been reported in unrelated individuals with mild PKU (Carluccio et al., 2013; Zekanowski et al. 1999; Bercovich et al., 2008).
Fulgent Genetics,Fulgent Genetics RCV000763292 SCV000893953 likely pathogenic Phenylketonuria 2018-10-31 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000763292 SCV000919908 likely pathogenic Phenylketonuria 2019-07-01 criteria provided, single submitter clinical testing Variant summary: PAH c.283A>T (p.Ile95Phe) results in a non-conservative amino acid change located in the ACT domain (IPR002912) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 251440 control chromosomes (gnomAD). c.283A>T has been reported in the literature in individuals affected with mild and moderate Phenylalanine Hydroxylase Deficiency (Phenylketonuria)( Bercovich_2008, Zekanowski_1999). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic and likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088890 SCV000119487 not provided not provided no assertion provided not provided

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