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.826A>G (p.Met276Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229794

102856 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: f085841b-65ba-4950-9a05-678a254062ce

Approved on: 2018-12-09

Published on: 2019-04-05

HGVS expressions

NM_000277.2:c.826A>G

NM_000277.2(PAH):c.826A>G (p.Met276Val)

NC_000012.12:g.102852831T>C

CM000674.2:g.102852831T>C

NC_000012.11:g.103246609T>C

CM000674.1:g.103246609T>C

NC_000012.10:g.101770739T>C

NG_008690.1:g.69772A>G

NG_008690.2:g.110580A>G

NM_000277.1:c.826A>G

NM_001354304.1:c.826A>G

NM_000277.3:c.826A>G

ENST00000307000.7:c.811A>G

ENST00000549247.6:n.585A>G

ENST00000553106.5:c.826A>G

Likely Pathogenic

PP4_Moderate PM2 PM3_Strong

PP3

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.826A>G (p.Met276Val) variant in PAH is absent from population databases. It has been identified in trans with pathogenic variants in two patients (A300S and R261Q; PMID: 16198137), and identified in an additional patient in which a defect in BH4 metabolism was excluded as a cause of elevated phenylalanine (PMID: 9634518). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3_strong.

PP4_Moderate

BH4 defect excluded. Single patient (Guldberg, 1998) PMID: 9634518

BH4 defect excluded in all patients PubMed:9634518

PM2

Absent from population databases

PM3_Strong

Two patients, A300S and R261Q (both pathogenic)(PMID: 16198137). Both with MHP

Two patients, both in trans with pathogenic variants (A300S and R261Q) PubMed:16198137

PP3

SIFT = Damaging Provean = Neutral REVEL = 0.786

Curation History

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