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]

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CA16020967

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 457b5ad6-23e5-475f-b9b0-f400ba230fe1

HGVS expressions

NM_001354304.2:c.1200G>T

NM_000277.1:c.1200G>T

NM_000277.2:c.1200G>T

NM_001354304.1:c.1200G>T

NM_000277.3:c.1200G>T

ENST00000307000.7:c.1185G>T

ENST00000549247.6:n.959G>T

ENST00000551114.2:n.862G>T

ENST00000553106.5:c.1200G>T

ENST00000635477.1:n.304G>T

ENST00000635528.1:n.715G>T

NC_000012.12:g.102840515C>A

CM000674.2:g.102840515C>A

NC_000012.11:g.103234293C>A

CM000674.1:g.103234293C>A

NC_000012.10:g.101758423C>A

NG_008690.1:g.82088G>T

NG_008690.2:g.122896G>T

Likely Pathogenic

PP3 PM2 PM5 PP4_Moderate

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1200G>T (p.Arg400Ser) variant in PAH has been reported in 2 Chinese patients, type of PKU not determined, serum Phe at least 120umol/L; BH4 deficiency excluded (PMID: 23932990; PP4_Moderate). This variant is at the same codon as c.1199G>C (p.R400T) - curated as Pathogenic by ClinGen PAH VCEP; c.1198del (p.Arg400fs) - reported as Pathogenic in ClinVar (VarID:102554); and c.1198A>C (p.Arg400=) - curated as VUS by ClinGen PAH VCEP (PM5). This variant is absent from population databases (PM2) and is predicted deleterious by SIFT, PolyPhen2, Mutation Taster, and REVEL = 0.901 (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP4_Moderate, PP3.

PP3

Predicted deleterious by SIFT, PolyPhen2, Mutation Taster, and REVEL = 0.901.

PM2

Absent from population databases.

PM5

At same codon as c.1199G>C (p.R400T) - curated as Pathogenic by ClinGen PAH VCEP; c.1199G>A (p.R400K) - reported as Likely Pathogenic in ClinVar (VarID:102561); c.1198del (p.Arg400fs) - reported as Pathogenic in ClinVar (VarID:102554); and c.1198A>C (p.Arg400=) - curated as VUS by ClinGen PAH VCEP

PP4_Moderate

PMID: 23932990 - R400S detected in 2 Chinese patients, type of PKU not determined, serum Phe at least 120umol/L; BH4 deficiency excluded via urinary pterin analysis and dihydropteridine reductase activity in erythrocytes

PubMed:23932990

Approved on: 2020-07-24

Published on: 2020-07-24

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