Clinical Genome Resources - Evidence Repository

Evidence Repository The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

• See Evidence submitted by expert panel for details.

Variant: NM_000277.2(PAH):c.1A>G (p.Met1Val)

• Curation Version - 1.0
• Curation History
• JSON LD for Version 1.0

CA114360

586 (ClinVar)

Gene: PAH Condition: phenylketonuria Inheritance Mode: Autosomal recessive inheritance Link to MONDO UUID: 89f04437-ed5d-4735-8c4a-a9b1d91d10ea Approved on: 2019-03-23 Published on: 2019-05-10

HGVS expressions

NM_000277.2:c.1A>G NM_000277.2(PAH):c.1A>G (p.Met1Val) NC_000012.12:g.102917130T>C CM000674.2:g.102917130T>C NC_000012.11:g.103310908T>C CM000674.1:g.103310908T>C NC_000012.10:g.101835038T>C NG_008690.1:g.5473A>G NG_008690.2:g.46281A>G NM_000277.1:c.1A>G NM_001354304.1:c.1A>G NM_000277.3:c.1A>G ENST00000307000.7:c.-147A>G ENST00000546844.1:c.1A>G ENST00000547319.1:n.312A>G ENST00000549111.5:n.97A>G ENST00000551337.5:c.1A>G ENST00000551988.5:n.90A>G ENST00000553106.5:c.1A>G ENST00000635500.1:n.29-4232A>G More

Pathogenic

Met criteria codes 4 PS3 PM3 PM2 PP4_Moderate Not Met criteria codes 1 PVS1

Evidence Links 2

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: PM2: gnomAD MAF=0.00002; PP4_Moderate: Seen in PKU patients. BH4 disorders ruled out. (PMID:2574002); PS3: <3% (PMID:9450897). PM3: Detected in trans with known pathogenic variants. 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: (PM2, PM3, PP4_Moderate, PS3). Updated to reflect new PVS1 recommendations. Met criteria codes PS3 <3% < 3 PAH enzyme activity as % of wild type. (p91023(B)/COS PubMed:9450897 PM3 Detected in trans with c.1315+1G>A (known pathogenic), and also in the homozygous state. A proband was homozygous for this mutation (A-to-G transition (met-val) in codon1]. In other probands, the codon1 mutation was inherited once with the splice junction mutation in exon 12 (c.1315+1G>A),and was inherited twice with a mutation on haplotype 1. PubMed:2574002 PM2 gnomAD MAF=0.00002 PP4_Moderate Seen in PKU patients. BH4 disorders ruled out. Analysis of RFLP haplotypes and mutations revealed a novel mutation, an A-to-G transition (met----val) in codon 1 (the translation-initiation codon). It occurred on 5 of the 18 mutant chromosomes. A proband homozygous for this mutation had the PKU phenotype. The appropriate biochemical tests were done to rule out disorders of tetrahydrobiopterin homeostasis. PubMed:2574002 Not Met criteria codes PVS1 Initiation codon variant 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. ¤ Powered by BCM's Genboree. ×

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