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]

Variant: NM_000277.3(PAH):c.745del (p.Leu249fs)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16020850

370982 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1c9d8c70-9dfc-4355-8ef0-9cc1b939866f

Approved on: 2021-05-15

Published on: 2021-12-12

HGVS expressions

NM_000277.3:c.745del

NM_000277.3(PAH):c.745del (p.Leu249fs)

NC_000012.12:g.102852912del

CM000674.2:g.102852912del

NC_000012.11:g.103246690del

CM000674.1:g.103246690del

NC_000012.10:g.101770820del

NG_008690.1:g.69691del

NG_008690.2:g.110499del

ENST00000553106.6:c.745del

ENST00000307000.7:c.730del

ENST00000549247.6:n.504del

ENST00000553106.5:c.745del

NM_000277.1:c.745del

NM_000277.2:c.745del

NM_001354304.1:c.745del

NM_001354304.2:c.745del

Pathogenic

PM3_Supporting PP4 PM2 PVS1

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.745del (p.Leu249fs) variant in PAH has been reported in 1 Chilean patient with mild PKU; Phe = 600-900umol/L (PMID: 29288420; PP4). This variant was detected with V388M - reported at Pathogenic in ClinVar (VarID:610, 7 submitters); phase not confirmed - 0.5 points (PMID: 29288420; PM3_supporting). This frameshift variant is predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon (Coding exon number 7 out of 13 coding exons; 7 out of total exons) (PVS1). This variant is absent from population databases (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4, PM3_supporting.

PM3_Supporting

PMID: 29288420 - L249fs detected with V388M - reported at Pathogenic in ClinVar (VarID:610, 7 submitters); phase not confirmed - 0.5 points

PP4

PMID: 29288420 - L249fs detected in 1 Chilean patient with mild PKU; Phe = 600-900umol/L

PM2

Variant absent from population databases.

PVS1

Frameshift variant, predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 7 out of 13 coding exons (7 out of total exons).

Curation History

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