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.190C>A (p.His64Asn)

CA229475

102620 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b8b9ffdf-a020-475b-8cc2-5e3e64b25c10

Approved on: 2018-12-10

Published on: 2019-04-06

HGVS expressions

NM_000277.2:c.190C>A

NM_000277.2(PAH):c.190C>A (p.His64Asn)

NC_000012.12:g.102894897G>T

CM000674.2:g.102894897G>T

NC_000012.11:g.103288675G>T

CM000674.1:g.103288675G>T

NC_000012.10:g.101812805G>T

NG_008690.1:g.27706C>A

NG_008690.2:g.68514C>A

NM_000277.1:c.190C>A

NM_001354304.1:c.190C>A

NM_000277.3:c.190C>A

ENST00000307000.7:c.175C>A

ENST00000546844.1:c.190C>A

ENST00000548677.2:n.277C>A

ENST00000548928.1:n.112C>A

ENST00000549111.5:n.286C>A

ENST00000550978.6:n.174C>A

ENST00000551337.5:c.190C>A

ENST00000551988.5:n.279C>A

ENST00000553106.5:c.190C>A

ENST00000635500.1:n.158C>A

Uncertain Significance

PP3 PM2 PP4_Moderate

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.190C>A (p.His64Asn) variant in PAH has been reported in a Danish mild PKU patient. Serum Phe levels exceeded 600 umol/L and other causes of hyperphenylalaninemia had been ruled out. It was In cis with p.T63P. PMID: 8406445. The c.190C>A variant is absent from ExAC, gnomAD, 1000G, and ESP. A deleterious effect is predicted in SIFT, Polyphen-2, and MutationTaster. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PP3.

PP3

Deleterious effect predicted in SIFT, Polyphen2, MutationTaster

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PP4_Moderate

H64N seen in Danish mild PKU patient. Serum Phe levels exceeded 600 umol/L and other causes of hyperphenylalaninemia had been ruled out. In cis with T63P. PMID: 8406445

Subjects included PKU patients and family members from 135 unrelated Danish families. Patients were diagnosed when their serum Phe levels exceeded 600 umol/L before treatment and when other causes of hyperphenylalaninemia had been ruled out. H64N seen on 1 allele, with T63P in cis. PubMed:8406445

PM5

only variant found in this codon in ClinVar

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.