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.520A>G (p.Ile174Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229603

102720 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 06092610-48ec-429d-b3f5-4e9cdd9d3209

Approved on: 2018-08-10

Published on: 2019-04-05

HGVS expressions

NM_000277.1:c.520A>G

NM_000277.1(PAH):c.520A>G (p.Ile174Val)

NC_000012.12:g.102855322T>C

CM000674.2:g.102855322T>C

NC_000012.11:g.103249100T>C

CM000674.1:g.103249100T>C

NC_000012.10:g.101773230T>C

NG_008690.1:g.67281A>G

NG_008690.2:g.108089A>G

NM_000277.2:c.520A>G

NM_001354304.1:c.520A>G

NM_000277.3:c.520A>G

ENST00000307000.7:c.505A>G

ENST00000549111.5:n.616A>G

ENST00000551988.5:n.541A>G

ENST00000553106.5:c.520A>G

Likely Pathogenic

PM3 PM2 PP3 PP4

PM5

Evidence Links 1

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: Not found in any population databases; PP3: All predictors agree--damaging; PM3: Single patient IVS4+5G>T (null) / I174V (Bercovich 2008 PMID 18299955) (PMID:18299955); PP4: Two independent patients (one in Zschocke (PMID 10394930) and one in Bercovich (PMID 18299955) with "PKU". While no specific levels are mentioned, they are followed in clinic and were diagnosed with Phe >120umol/L. BH4 defect WAS NOT excluded in either paper.. In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PP3, PM3, PP4).

PM3

Single patient IVS4+5G>T (null) / I174V (Bercovich 2008 PMID 18299955)

Single patient: IVS4+5G>T / I174V – mild PKU (plasma phe 6.5-10mg/dl and tolerate 400-600mg/day of dietary Phe)—no specific level listed PubMed:18299955

PM2

Not found in any population databases

PP3

All predictors agree--damaging

PP4

Two independent patients (one in Zschocke (PMID 10394930) and one in Bercovich (PMID 18299955) with "PKU". While no specific levels are mentioned, they are followed in clinic and were diagnosed with Phe >120umol/L. BH4 defect WAS NOT excluded in either paper.

PM5

VUS at c.521

Curation History

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