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_000277.1(PAH):c.609C>G (p.Cys203Trp)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229647

102755 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0aa6ba38-c16b-4adc-86a5-616bdef1424f

Approved on: 2020-02-22

Published on: 2021-06-11

HGVS expressions

NM_000277.1:c.609C>G

NM_000277.1(PAH):c.609C>G (p.Cys203Trp)

NC_000012.12:g.102855233G>C

CM000674.2:g.102855233G>C

NC_000012.11:g.103249011G>C

CM000674.1:g.103249011G>C

NC_000012.10:g.101773141G>C

NG_008690.1:g.67370C>G

NG_008690.2:g.108178C>G

ENST00000553106.6:c.609C>G

ENST00000307000.7:c.594C>G

ENST00000549111.5:n.705C>G

ENST00000553106.5:c.609C>G

NM_000277.2:c.609C>G

NM_001354304.1:c.609C>G

NM_000277.3:c.609C>G

NM_001354304.2:c.609C>G

Likely Pathogenic

PP4_Moderate PM3_Supporting PP3 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.609C>G (p.Cys203Trp) variant in PAH has been reported in 1 individual with PKU (BH4 deficiency excluded) detected with pathogenic variant c.1315+1G>A (P 13 submitters) parental analysis not performed. (PMID: 23430918). This variant has extremely low frequency in 1000G (MAF=0.0004) and is absent from gnomAD. Computational evidence supports a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3_supporting, PP3.

PP4_Moderate

detected in a patient with PKU. primary BH4 deficiency excluded. PMID: 23430918

PM3_Supporting

Detected with c.1315+1G>A (P 13 submitters). parental analysis not performed

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster, REVEL=0.91

PM2

MAF=0.0004 in 1000G, absent in ExAC, gnomAD, ESP

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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