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

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

CA229329

102514 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

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

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 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.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

PM2

Absent from controls.

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

Approved on: 2020-06-05

Published on: 2020-06-05

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