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>G (p.Lys341Arg)

CA229275

102472 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3b7cbd7c-5664-4f39-ae69-26101308d58e

HGVS expressions

NM_000277.3:c.1022A>G

NM_000277.3(PAH):c.1022A>G (p.Lys341Arg)

NC_000012.12:g.102844379T>C

CM000674.2:g.102844379T>C

NC_000012.11:g.103238157T>C

CM000674.1:g.103238157T>C

NC_000012.10:g.101762287T>C

NG_008690.1:g.78224A>G

NG_008690.2:g.119032A>G

ENST00000553106.6:c.1022A>G

ENST00000307000.7:c.1007A>G

ENST00000549247.6:n.781A>G

ENST00000551114.2:n.684A>G

ENST00000553106.5:c.1022A>G

ENST00000635477.1:n.126A>G

ENST00000635528.1:n.537A>G

NM_000277.1:c.1022A>G

NM_000277.2:c.1022A>G

NM_001354304.1:c.1022A>G

NM_001354304.2:c.1022A>G

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.1022A>G (p.Lys341Arg) variant in PAH has not been reported in a patient with PAH deficiency (to our knowledge). It was submitted to the PAHdb/McGill by Cadiou in 1994. This variant is absent from controls in ExAC, gnomAD, 1000 Genomes, and ESP. There are conflicting interpretations of pathogenicity: SIFT (T); PolyPhen2 (P); MutationTaster (D), REVEL=0.831. 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 interpretations of pathogenicity: SIFT (T); PolyPhen2 (P); MutationTaster (D), REVEL=0.831.

PM5

L341T interpreted as VUS by PAH VCEP

Approved on: 2019-12-15

Published on: 2021-05-14

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