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.1101G>A (p.Leu367=)

CA229346

102526 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7e24b8a9-c6fa-4c49-8a3b-42729f9e6f4f

HGVS expressions

NM_000277.2:c.1101G>A

NM_000277.2(PAH):c.1101G>A (p.Leu367=)

NC_000012.12:g.102843744C>T

CM000674.2:g.102843744C>T

NC_000012.11:g.103237522C>T

CM000674.1:g.103237522C>T

NC_000012.10:g.101761652C>T

NG_008690.1:g.78859G>A

NG_008690.2:g.119667G>A

ENST00000553106.6:c.1101G>A

ENST00000307000.7:c.1086G>A

ENST00000549247.6:n.860G>A

ENST00000551114.2:n.763G>A

ENST00000553106.5:c.1101G>A

ENST00000635477.1:n.205G>A

ENST00000635528.1:n.616G>A

NM_000277.1:c.1101G>A

NM_001354304.1:c.1101G>A

NM_000277.3:c.1101G>A

NM_001354304.2:c.1101G>A

NM_000277.3(PAH):c.1101G>A (p.Leu367=)

Uncertain Significance

PP4 PP3 PM3 PM2_Supporting

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1101G>A (p.Leu367=) variant in PAH is reported in an individual with Classic PKU, in trans with p.R243Q. (PMID: 16256386) This variant is absent in population databases. Two splicing algorthms predict a deleterious effect (Human splicing finder: potential alteration of splicing; MaxEnt scan: +571.94% Variation). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2_supporting, PM3, PP4, PP3.

PP4

Seen in an individual with Classic PKU. PMID: 16256386

PP3

human splicing finder predicts potential alteration of splicing. MaxEnt scan +571.94% Variation.

PM3

In trans with R243Q. Maternal or paternal inheritance of mutations was determined particularly for patients with novel mutation when parental DNA was available. PMID: 16256386

PM2_Supporting

absent from gnomAD v2.1.1

Approved on: 2023-07-23

Published on: 2023-07-23

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