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]

Link to SEPIO compliant JSON-LD document

CA386296582

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0c78dc36-0ebe-4bea-9d50-6ff0856bbb8f

HGVS expressions

NM_001354304.2:c.679C>G

NC_000012.12:g.102855163G>C

CM000674.2:g.102855163G>C

NC_000012.11:g.103248941G>C

CM000674.1:g.103248941G>C

NC_000012.10:g.101773071G>C

NG_008690.1:g.67440C>G

NG_008690.2:g.108248C>G

NM_000277.1:c.679C>G

NM_000277.2:c.679C>G

NM_001354304.1:c.679C>G

NM_000277.3:c.679C>G

ENST00000307000.7:c.664C>G

ENST00000549111.5:n.775C>G

ENST00000553106.5:c.679C>G

Likely Pathogenic

PP3 PP4 PM2 PM3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.679C>G (p.Leu227Val) variant in PAH was reported in trans with pathogenic variant p.Arg243Gln in 1 patient with PAH deficiency (1134μmol/L Phe) (PMID: 28982351). Computational evidence for this missense variant is predicted to be damaging (SIFT), probably damaging (PolyPhen2), and disease causing (MutationTaster). This variant is absent from population databases gnomAD, 1000 Genomes, and ESP. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PM3, PP4.

PP3

Computational evidence for this missense variant is predicted to be damaging (SIFT), probably damaging (PolyPhen2), and disease causing (MutationTaster).

PP4

This variant was documented 1 time in a patient with PAH deficiency (1134μmol/L Phe) in the Han Chinese population. Patients with BH4 cofactor deficiency were excluded by BH4 loading. PMID: 28982351

PM2

This variant is absent from population databases gnomAD,1000 Genomes, and ESP

PM3

This variant was detected in trans with the pathogenic PAH variant p.Arg243Gln (1.0pt) PMID: 28982351

Approved on: 2020-12-09

Published on: 2021-01-15

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