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.1068C>A (p.Tyr356Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA273107

92729 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6f390ad4-1675-4f3f-9b2d-eb81f608dc3b

Approved on: 2018-08-13

Published on: 2019-04-06

HGVS expressions

NM_000277.2:c.1068C>A

NM_000277.2(PAH):c.1068C>A (p.Tyr356Ter)

NC_000012.12:g.102843777G>T

CM000674.2:g.102843777G>T

NC_000012.11:g.103237555G>T

CM000674.1:g.103237555G>T

NC_000012.10:g.101761685G>T

NG_008690.1:g.78826C>A

NG_008690.2:g.119634C>A

NM_000277.1:c.1068C>A

NM_001354304.1:c.1068C>A

NM_000277.3:c.1068C>A

ENST00000307000.7:c.1053C>A

ENST00000549247.6:n.827C>A

ENST00000551114.2:n.730C>A

ENST00000553106.5:c.1068C>A

ENST00000635477.1:n.172C>A

ENST00000635528.1:n.583C>A

Pathogenic

PVS1 PP4_Moderate PM2 PM3_Strong

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: PVS1: Nonsense variant; PM2: gnomAD MAF 0.00017; PP4_Moderate: Detected in PKU patients (PMID:25894915); PM3_Strong: in trans with p.W326X (Pathogenic), and IVS4-1G>A (Pathogenic). (PMID:25894915). In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PVS1, PM2, PP4_Moderate, PM3_Strong).

PVS1

Nonsense variant

PP4_Moderate

Detected in PKU patients

BH4 defect excluded in all patients PubMed:25894915

PM2

gnomAD MAF 0.00017

PM3_Strong

in trans with p.W326X (Pathogenic), and IVS4-1G>A (Pathogenic).

Identified in several patients in this cohort in trans with p.W326X (Pathogenic), p.R158W, p.G257V, and IVS4-1G>A (Pathogenic). PubMed:25894915

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.