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_000277.2(PAH):c.718T>G (p.Phe240Val)

CA229713

102801 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 91df5c40-1e87-49a7-b02e-2cb85486ce49

HGVS expressions

NM_000277.2:c.718T>G

NM_000277.2(PAH):c.718T>G (p.Phe240Val)

NC_000012.12:g.102852939A>C

CM000674.2:g.102852939A>C

NC_000012.11:g.103246717A>C

CM000674.1:g.103246717A>C

NC_000012.10:g.101770847A>C

NG_008690.1:g.69664T>G

NG_008690.2:g.110472T>G

ENST00000553106.6:c.718T>G

ENST00000307000.7:c.703T>G

ENST00000549247.6:n.477T>G

ENST00000553106.5:c.718T>G

NM_000277.1:c.718T>G

NM_001354304.1:c.718T>G

NM_000277.3:c.718T>G

NM_001354304.2:c.718T>G

NM_000277.3(PAH):c.718T>G (p.Phe240Val)

Uncertain Significance

PP3 PM2

PM1 PM5

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.718T>G (p.Phe240Val) variant in PAH has not been reported in the literature detected in an affected patient to our knowledge. This variant is absent from ExAC, gnomAD, 1000G, and ESP. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.978. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3.

PP3

Predicted deleterious in SIFT, Polyphen2, MutationTaster. REVEL=0.978

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PM1

Close to active site area as well as several Phe's - stacks onto Phe294. Disrupted on substitution to Val. PMID: 10527663

Close to active site area as well as several Phe's - stacks onto Phe294. Disrupted on substitution to Val. PubMed:10527663

PM5

F240S, no clinical assertion in ClinVar, LP by PAH VCEP

Approved on: 2020-11-09

Published on: 2022-02-20

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