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_000277.1:c.1301C>T

CA16020990

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: aa9f120b-6559-4c5b-9976-8f1c79750adc

HGVS expressions

NM_000277.1:c.1301C>T

NC_000012.12:g.102840414G>A

CM000674.2:g.102840414G>A

NC_000012.11:g.103234192G>A

CM000674.1:g.103234192G>A

NC_000012.10:g.101758322G>A

NG_008690.1:g.82189C>T

NG_008690.2:g.122997C>T

ENST00000553106.6:c.1301C>T

ENST00000307000.7:c.1286C>T

ENST00000551114.2:n.963C>T

ENST00000553106.5:c.1301C>T

ENST00000635477.1:n.405C>T

ENST00000635528.1:n.816C>T

NM_000277.2:c.1301C>T

NM_001354304.1:c.1301C>T

NM_000277.3:c.1301C>T

NM_001354304.2:c.1301C>T

Likely Pathogenic

PP4 PM5 PM2 PM3_Supporting

PP3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1301C>T (p.Ala434Val) variant in PAH has been reported in 1 individual with classic PKU detected with pathogenic variant p.R243X (PMID: 24350308). This variant is absent in population databases. Another missense change at the same amino acid (p.Ala434Asp) is likely pathogenic by 1 submitter and pathogenic by PAH VCEP. Computational evidence is conflicting. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PM3_supporting, PP4.

PP4

A434V seen on 1 allele of a classic PKU patient. BH4 deficiency not assessed/reported. PMID: 24350308

1286 PKU-patients were genotyped. A434V seen on 1 allele of a classic PKU patient. PubMed:24350308

PM5

A434D (VarID 102586) is likely pathogenic in ClinVar, and Pathogenic based on ClinGen PAH VCEP

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PM3_Supporting

Found with R243X, parental testing not reported PMID: 24350308

A434V seen with p.R243* in 1 patient (VarID 588, Pathogenic) PubMed:24350308

PP3

Conflicting predictions of pathogenicity: tolerated/benign in SIFT+Polyphen2, Disease causing in MutationTaster

Approved on: 2020-08-13

Published on: 2021-11-21

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.