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.1022A>C (p.Lys341Thr)

CA229274

102471 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 00dd024a-b222-4113-9e07-5c75e4156154

HGVS expressions

NM_000277.3:c.1022A>C

NM_000277.3(PAH):c.1022A>C (p.Lys341Thr)

ENST00000553106.6:c.1022A>C

ENST00000307000.7:c.1007A>C

ENST00000549247.6:n.781A>C

ENST00000551114.2:n.684A>C

ENST00000553106.5:c.1022A>C

ENST00000635477.1:n.126A>C

ENST00000635528.1:n.537A>C

NM_000277.1:c.1022A>C

NM_000277.2:c.1022A>C

NM_001354304.1:c.1022A>C

NM_001354304.2:c.1022A>C

NC_000012.12:g.102844379T>G

CM000674.2:g.102844379T>G

NC_000012.11:g.103238157T>G

CM000674.1:g.103238157T>G

NC_000012.10:g.101762287T>G

NG_008690.1:g.78224A>C

NG_008690.2:g.119032A>C

Uncertain Significance

PP4 PP3 PM2

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.1022A>C (p.Lys341Thr) variant in PAH has been reported in a patient with PKU (BH4 deficiency not assessed, PMID: 9012412). This variant is absent from controls in ExAC, gnomAD, 1000 Genomes, and ESP. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.945. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PP4.

PP4

Reported in a patient with PKU. PMID: 9012412

PP3

Deleterious effect predicted in SIFT, PolyPhen2, MutationTaster. REVEL=0.945.

PM2

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

PM5

K341R has no interpretation in ClinVar

Approved on: 2019-12-15

Published on: 2021-05-14

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