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_001354304.2:c.679C>G

CA386296582

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

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

Approved on: 2020-12-09

Published on: 2021-01-15

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

PM3 PM2 PP3 PP4

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.

PM3

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

PM2

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

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

Curation History

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