Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_000277.2(PAH):c.801G>C (p.Gln267His)

CA229771

102840 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 88cc7aae-46c6-4cce-a1fb-557f845bdb01

HGVS expressions

NM_000277.2:c.801G>C

NM_000277.2(PAH):c.801G>C (p.Gln267His)

NC_000012.12:g.102852856C>G

CM000674.2:g.102852856C>G

NC_000012.11:g.103246634C>G

CM000674.1:g.103246634C>G

NC_000012.10:g.101770764C>G

NG_008690.1:g.69747G>C

NG_008690.2:g.110555G>C

NM_000277.1:c.801G>C

NM_001354304.1:c.801G>C

NM_000277.3:c.801G>C

ENST00000307000.7:c.786G>C

ENST00000549247.6:n.560G>C

ENST00000553106.5:c.801G>C

Likely Pathogenic

PP3 PP4 PM3 PM2

PM5

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.801G>C (p.Gln267His) variant in PAH has been reported in 1 Chinese patient with classical PKU. BH4 deficiencies were not assessed. PMID: 16256386, 19915519. It was detected with a known pathogenic variant p.R252Q. PMID: 16256386. It is absent from population databases. It is predicted deleterious in SIFT, Polyphen2, MutationTaster, and REVEL=0.952. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP3, PP4.

PP3

Predicted deleterious in SIFT, Polyphen2, MutationTaster. REVEL=0.952.

PP4

Q267H found in 1 Chinese patient with classical PKU. BH4 deficiencies not assessed. PMID: 16256386, 19915519.

Systematically investigated 13 exons and their surrounding introns of the phenylalanine hydroxylase (PAH) gene in 212 unrelated patients using PCR and direct sequencing. Possibly same patient as Song et al, but no genotype reported. PubMed:19915519

By using PCR/SSCP and DNA sequencing, all exons of PAH gene in the 185 unrelated patients with PKU from Northern China were studied. Fifteen novel mutations were identified in this study: including Q267H, Q267E. Each of them occurs at very low frequency (0.3-1.1%). Q267H was found in 1 classical PKU patient. PAH deficiency was diagnosed by conventional biochemical methods. PubMed:16256386

PM3

Q267H was detected with R252Q PMID: 16256386

Patient genotype: R252Q (VarID 102824, Pathogenic)+ Q267H. Maternal or paternal inheritance of mutations was determined particularly for patients with novel mutation when parental DNA was available. PubMed:16256386

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PM5

2 other variants at this codon in ClinVar. Q276L is likely pathogenic

Approved on: 2018-12-10

Published on: 2019-04-05

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