ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.922C>G (p.Leu308Val)

dbSNP: rs62642095
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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 RCV004821979 SCV005442790 likely pathogenic Phenylketonuria 2024-09-06 reviewed by expert panel curation The NM_000277.1(PAH):c.922C>G (p.Leu308Val) variant is a missense variant in exon 9/13 of PAH. The variant has been found to reduce PAH enzymatic activity to 15-19% versus wild type PAH enzyme in transfected COS cells (PMID: 18590700). The variant has been previously reported in confirmed trans with the c.1315+1G>A variant (Pathogenic per ClinGen PAH VCEP) in a patient with mild PKU (plasma Phe 600-900 umol/L); BH4 deficiency does not appear to have been excluded (PMID: 26542770). The variant is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP. The variant is predicted damaging by multiple in-silico missense predictors, including REVEL (REVEL score 0.892). Classification: Likely Pathogenic Supporting Criteria: PS3_supporting; PM2_supporting; PM3; PP4; PP3_moderate
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089158 SCV000119772 not provided not provided no assertion provided not provided

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