ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.870T>G (p.His290Gln)

dbSNP: rs751203209
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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 RCV000674910 SCV002032230 likely pathogenic Phenylketonuria 2021-12-12 reviewed by expert panel curation The c.870T>G (p.His290Gln) variant in PAH has been reported in one patient with classic PKU (BH4 deficiency not excluded; PP4; PMID: 26210745). It was detected with known pathogenic variant p.R261Q, but parental testing was not reported/performed. Functional studies show low but measurable activities for tyrosine formation and greatly decreased the affinity for iron (PMID: 18477464). This variant is absent from 1000G, ESP, ExAC and gnomAD. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.924. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PP3, PM3_supporting, PS3_supporting.
Counsyl RCV000674910 SCV000800322 uncertain significance Phenylketonuria 2018-05-31 criteria provided, single submitter clinical testing

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