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.289A>C (p.Ile97Leu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA6748987

376937 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: c5437297-1b67-4097-ba03-479a5330c664

Approved on: 2018-08-07

Published on: 2019-04-06

HGVS expressions

NM_000277.2:c.289A>C

NM_000277.2(PAH):c.289A>C (p.Ile97Leu)

NC_000012.12:g.102894798T>G

CM000674.2:g.102894798T>G

NC_000012.11:g.103288576T>G

CM000674.1:g.103288576T>G

NC_000012.10:g.101812706T>G

NG_008690.1:g.27805A>C

NG_008690.2:g.68613A>C

NM_000277.1:c.289A>C

NM_001354304.1:c.289A>C

NM_000277.3:c.289A>C

ENST00000307000.7:c.274A>C

ENST00000546844.1:c.289A>C

ENST00000548928.1:n.211A>C

ENST00000549111.5:n.385A>C

ENST00000550978.6:n.273A>C

ENST00000551337.5:c.289A>C

ENST00000551988.5:n.378A>C

ENST00000553106.5:c.289A>C

Uncertain Significance

PP4 BP4

PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: BP4: Tolerated in SIFT, benign in Polyphen-2, Polymorphism in MutationTaster. REVEL=0.511; PP4: Seen in patient with mild HPA (PMID:17627389). In summary this variant meets criteria to be classified as uncertain significance for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (BP4, PP4).

PP4

Seen in patient with mild HPA

Patient with mild HPA had I97L, but second allele not identified. PubMed:17627389

BP4

Tolerated in SIFT, benign in Polyphen-2, Polymorphism in MutationTaster. REVEL=0.511

PM2

gnomAD MAF: 0.00187

Curation History

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