ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.935G>A (p.Gly312Asp)

dbSNP: rs62642915
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV001269049 SCV001448242 likely pathogenic Phenylketonuria 2020-07-27 reviewed by expert panel curation The NM_000277.1(PAH):c.935G>A (p.Gly312Asp) variant is a missense variant in exon 9/13 of PAH. It has been reported in at least 3 PKU cases in presumed trans with other Pathogenic variants (PM3; 1.5 points total), in two of whom BH4 deficiency was excluded (PP4_Moderate). It has been previously reported in presumed trans with the p.R241C variant (Pathogenic per ClinGen PAH VCEP) in two cases with mild PKU (plasma Phe 600–1200 μmol/L) and BH4 deficiency excluded (PMID: 30459323). It has also been reported in presumed trans with the p. R408W variant (Pathogenic by ClinGen PAH VCEP) in a patient with classic PKU and with undefined BH4 responsiveness. The variant is absent from ethnically diverse control databases, including gnomAD/ExAC, 1000 Genomes, and ESP (PM2). The variant is predicted damaging by multiple in-silico missense predictors, including REVEL (REVEL score 0.958) (PP3). Classification: Likely Pathogenic Supporting Criteria: PM2; PM3; PP4_Moderate; PP3
Baylor Genetics RCV001269049 SCV004209669 likely pathogenic Phenylketonuria 2023-05-16 criteria provided, single submitter clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089165 SCV000119780 not provided not provided no assertion provided not provided

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