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_000277.3:c.1105C>G

CA16020941

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

UUID: 6c5abef4-0425-4068-89b1-32c3730a4636

Approved on: 2020-01-20

Published on: 2021-09-06

HGVS expressions

NM_000277.3:c.1105C>G

ENST00000553106.6:c.1105C>G

ENST00000307000.7:c.1090C>G

ENST00000549247.6:n.864C>G

ENST00000551114.2:n.767C>G

ENST00000553106.5:c.1105C>G

ENST00000635477.1:n.209C>G

ENST00000635528.1:n.620C>G

NM_000277.1:c.1105C>G

NM_000277.2:c.1105C>G

NM_001354304.1:c.1105C>G

NM_001354304.2:c.1105C>G

NC_000012.12:g.102843740G>C

CM000674.2:g.102843740G>C

NC_000012.11:g.103237518G>C

CM000674.1:g.103237518G>C

NC_000012.10:g.101761648G>C

NG_008690.1:g.78863C>G

NG_008690.2:g.119671C>G

Likely Pathogenic

PP4_Moderate PM2 PM3

PP3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1105C>G (p.Leu369Val) variant in PAH has been reported in 2 individuals with mild HPA (BH4 deficiency excluded). (PP4_Moderate; PMID: 18299955). This variant is absent in population databases (PM2). This variant was detected with pathogenic variants p.T380M and p.V230I (Parental analysis not reported, PM3). Computational evidence is conflicting. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3.

PP4_Moderate

Detected in 2 patients with mild HPA. BH4 deficiency excluded. PMID: 18299955

PM2

Absent from controls in ExAC, gnomAD, 1000 Genomes, ESP

PM3

Detected with T380M (P, multiple submitters) and V230I (P/LP). Parental analysis not reported.

PP3

Computational evidence is conflicting: deleterious in SIFT; benign in PolyPhen2, MutationTaster, REVEL=0.598.

Curation History

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