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_000277.3(PAH):c.1019T>C (p.Ile340Thr)

CA229270

102469 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 53774688-6857-451a-bca4-eb3b7286e812

HGVS expressions

NM_000277.3:c.1019T>C

NM_000277.3(PAH):c.1019T>C (p.Ile340Thr)

ENST00000553106.6:c.1019T>C

ENST00000307000.7:c.1004T>C

ENST00000549247.6:n.778T>C

ENST00000551114.2:n.681T>C

ENST00000553106.5:c.1019T>C

ENST00000635477.1:n.123T>C

ENST00000635528.1:n.534T>C

NM_000277.1:c.1019T>C

NM_000277.2:c.1019T>C

NM_001354304.1:c.1019T>C

NM_001354304.2:c.1019T>C

NC_000012.12:g.102844382A>G

CM000674.2:g.102844382A>G

NC_000012.11:g.103238160A>G

CM000674.1:g.103238160A>G

NC_000012.10:g.101762290A>G

NG_008690.1:g.78221T>C

NG_008690.2:g.119029T>C

Uncertain Significance

PM2

PP3 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.1019T>C (p.Ile340Thr) variant in PAH has been not been reported in a patient with PAH deficiency (to our knowledge). It was reported to the PAHdb (McGill) by Tyfield in 2003. This variant is absent from controls in ExAC, gnomAD, 1000 Genomes, and ESP. There are conflicting predictions of pathogenicity: SIFT (T); PolyPhen2 (B); REVEL=0.731; MutationTaster (D). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2.

PM2

Absent from controls in ExAC, gnomAD, 1000 Genomes, or ESP

PP3

Conflicting predictions of pathogenicity: SIFT (T); PolyPhen2 (B); REVEL=0.731; MutationTaster (D).

PM5

The current variant is the only variant found in this codon in ClinVar.

Approved on: 2019-12-15

Published on: 2021-05-14

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