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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000277.3(PAH):c.1001G>C (p.Cys334Ser)

CA229263

102464 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: bffa79b5-d67a-4083-b12e-2d5e84071018

HGVS expressions

NM_000277.3:c.1001G>C

NM_000277.3(PAH):c.1001G>C (p.Cys334Ser)

NC_000012.12:g.102844400C>G

CM000674.2:g.102844400C>G

NC_000012.11:g.103238178C>G

CM000674.1:g.103238178C>G

NC_000012.10:g.101762308C>G

NG_008690.1:g.78203G>C

NG_008690.2:g.119011G>C

ENST00000307000.7:c.986G>C

ENST00000553106.5:c.1001G>C

NM_000277.1:c.1001G>C

NM_000277.2:c.1001G>C

NM_001354304.1:c.1001G>C

NM_001354304.2:c.1001G>C

Uncertain Significance

PP4 PP3 PM3_Supporting PM2

PM5

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1001G>C (p.Cys334Ser) variant in PAH has been reported in 2 patients with mild PKU/HPA. (BH4 deficiency not ruled out. PMID: 8632937, 10693064). It was detected with pathogenic variant p.F299C (PM3_supporting). This variant is absent from controls in ExAC, gnomAD, 1000 Genomes, and ESP. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.976. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PP4, PM3_supporting.

PP4

Detected in multiple patients with mild PKU/HPA. BH4 deficiency not ruled out. PMID: 8632937, 10693064

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster. REVEL=0.976.

PM3_Supporting

Detected with F299C (P, 5 submitters), parental analysis not reported

PM2

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

PM5

The current variant is the only variant found in this codon in ClinVar.

Approved on: 2019-12-15

Published on: 2021-04-09

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