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

CA16020941

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6c5abef4-0425-4068-89b1-32c3730a4636

HGVS expressions

NM_000277.3:c.1105C>G

ENST00000553106.6:c.1105C>G

ENST00000307000.7:c.1090C>G

ENST00000549247.6:n.864C>G

ENST00000551114.2:n.767C>G

ENST00000553106.5:c.1105C>G

ENST00000635477.1:n.209C>G

ENST00000635528.1:n.620C>G

NM_000277.1:c.1105C>G

NM_000277.2:c.1105C>G

NM_001354304.1:c.1105C>G

NM_001354304.2:c.1105C>G

NC_000012.12:g.102843740G>C

CM000674.2:g.102843740G>C

NC_000012.11:g.103237518G>C

CM000674.1:g.103237518G>C

NC_000012.10:g.101761648G>C

NG_008690.1:g.78863C>G

NG_008690.2:g.119671C>G

Likely Pathogenic

PM3 PM2 PP4_Moderate

PP3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1105C>G (p.Leu369Val) variant in PAH has been reported in 2 individuals with mild HPA (BH4 deficiency excluded). (PP4_Moderate; PMID: 18299955). This variant is absent in population databases (PM2). This variant was detected with pathogenic variants p.T380M and p.V230I (Parental analysis not reported, PM3). Computational evidence is conflicting. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3.

PM3

Detected with T380M (P, multiple submitters) and V230I (P/LP). Parental analysis not reported.

PM2

Absent from controls in ExAC, gnomAD, 1000 Genomes, ESP

PP4_Moderate

Detected in 2 patients with mild HPA. BH4 deficiency excluded. PMID: 18299955

PP3

Computational evidence is conflicting: deleterious in SIFT; benign in PolyPhen2, MutationTaster, REVEL=0.598.

Approved on: 2020-01-20

Published on: 2021-09-06

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.