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.1069T>G (p.Cys357Gly)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229329

102514 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0977199f-62f0-46c1-b092-5206646c9ea4

Approved on: 2020-06-05

Published on: 2020-06-05

HGVS expressions

NM_000277.2:c.1069T>G

NM_000277.2(PAH):c.1069T>G (p.Cys357Gly)

NM_000277.1:c.1069T>G

NM_001354304.1:c.1069T>G

NM_000277.3:c.1069T>G

NM_001354304.2:c.1069T>G

ENST00000307000.7:c.1054T>G

ENST00000549247.6:n.828T>G

ENST00000551114.2:n.731T>G

ENST00000553106.5:c.1069T>G

ENST00000635477.1:n.173T>G

ENST00000635528.1:n.584T>G

NC_000012.12:g.102843776A>C

CM000674.2:g.102843776A>C

NC_000012.11:g.103237554A>C

CM000674.1:g.103237554A>C

NC_000012.10:g.101761684A>C

NG_008690.1:g.78827T>G

NG_008690.2:g.119635T>G

Likely Pathogenic

PP3 PP4 PM3 PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1069T>G (p.Cys357Gly) variant in PAH has been reported in 1 individual with classic PKU in trans with pathogenic variant p.R176X (PMID: 11139255). This variant is absent in population databases. Computational evidence supports a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3, PP3.

PP3

Predicted deleterious by PolyPhen, MutationTaster, SIFT.

PP4

Seen in an individual with classic PKU, in trans with R176X (pathogenic). PHE level >4 for all patients in study.

Seen in an individual with classic PKU, in trans with R176X (pathogenic). PHE level >4 for all patients in study. PubMed:11139255

PM3

in trans with R176X (pathogenic), paternal allele PMID: 11139255

Seen in an individual with classic PKU, in trans with R176X (pathogenic). PHE level >4 for all patients in study. PubMed:11139255

PM2

Absent from controls.

Curation History

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.