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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CA16020901

619151 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: a61018fa-1019-4c4e-8bb6-1f469dc6e5de

Approved on: 2018-12-09

Published on: 2019-04-06

HGVS expressions

NM_000277.1:c.934G>C

NC_000012.12:g.102846930C>G

CM000674.2:g.102846930C>G

NC_000012.11:g.103240708C>G

CM000674.1:g.103240708C>G

NC_000012.10:g.101764838C>G

NG_008690.1:g.75673G>C

NG_008690.2:g.116481G>C

NM_000277.2:c.934G>C

NM_001354304.1:c.934G>C

NM_000277.3:c.934G>C

ENST00000307000.7:c.919G>C

ENST00000549247.6:n.693G>C

ENST00000551114.2:n.596G>C

ENST00000553106.5:c.934G>C

ENST00000635477.1:n.74-2499G>C

ENST00000635528.1:n.449G>C

Uncertain Significance

PP3 PP4 PM2

PM3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.934G>C (p.Gly312Arg) variant in PAH is absent from population databases, and predicted damaging by in silico algorithms. It is identified in a single patient with phenylketonuria, in trans with a VUS (IVS8-7A>G) Defect in BH4 metabolism was not excluded in this publication (Bashyam, 2014. PMID: 24130151). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PP3.

PP3

All agree deleterious effect. REVEL=0.95

PP4

Single patient Phe 2129umol/L, but BH4 not excluded

Single patient, Phe 2129umol/L but BH4 not excluded PubMed:24130151

PM2

Absent from population databases

PM3

IVS8-7A>G (VUS) . PMID: 24130151

single patient, second variant IVS8-7A>G (in clinvar, but not defined) PubMed:24130151

Curation History

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