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]

Variant: NM_000277.2(PAH):c.704A>C (p.Gln235Pro)

Curation Version - 1.2
Curation History
JSON LD for Version 1.2

CA229700

102791 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 46b753d2-0a95-47e7-9845-a289073f7aa6

Approved on: 2020-11-09

Published on: 2024-11-18

HGVS expressions

NM_000277.2:c.704A>C

NM_000277.2(PAH):c.704A>C (p.Gln235Pro)

NC_000012.12:g.102855138T>G

CM000674.2:g.102855138T>G

NC_000012.11:g.103248916T>G

CM000674.1:g.103248916T>G

NC_000012.10:g.101773046T>G

NG_008690.1:g.67465A>C

NG_008690.2:g.108273A>C

ENST00000553106.6:c.704A>C

ENST00000307000.7:c.689A>C

ENST00000549111.5:n.800A>C

ENST00000553106.5:c.704A>C

NM_000277.1:c.704A>C

NM_001354304.1:c.704A>C

NM_000277.3:c.704A>C

NM_001354304.2:c.704A>C

Uncertain Significance

PP3 PP4 PM2 PM3_Supporting

PM5 PS1

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.704A>C (p.Gln235Pro) variant in PAH has been reported in a Chinese patient with classical PKU, detected with pathogenic variant c.442-1G>A (PMID: 16256386) This variant is absent in population databases. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.947. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3_supporting, PP3, PP4.

PP3

Predicted deleterious in SIFT, Polyphen2, MutationTaster. REVEL=0.947

PP4

Q235P seen in 1 PKU patient. BH4 deficiency not excluded. PMID: 16256386

All exons of PAH gene in 185 unrelated patients with PKU from Northern China were studied. Q235P seen on 1 allele. PubMed:16256386

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PM3_Supporting

Q235P/IVS4-1G>A in 1 patient. Maternal or paternal inheritance of mutations was determined when parental DNA was available. PMID: 16256386

Q235P seen with IVS4-1G>A (VarID 594, pathogenic) in 1 patient. PubMed:16256386

PM5

Only variant in this codon in ClinVar

PS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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