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_000277.2(PAH):c.1092_1106del (p.Leu365_Leu369del)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229339

620 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 5a4488b7-d663-48dd-bf7b-106a42346d82

Approved on: 2019-05-04

Published on: 2021-02-26

HGVS expressions

NM_000277.2:c.1092_1106del

NM_000277.2(PAH):c.1092_1106del (p.Leu365_Leu369del)

NC_000012.12:g.102843739_102843753del

CM000674.2:g.102843739_102843753del

NC_000012.11:g.103237517_103237531del

CM000674.1:g.103237517_103237531del

NC_000012.10:g.101761647_101761661del

NG_008690.1:g.78846_78860del

NG_008690.2:g.119654_119668del

ENST00000307000.7:c.1073_1087del

ENST00000553106.5:c.1088_1102del

NM_000277.1:c.1088_1102del

NM_000277.2:c.1088_1102del

NM_001354304.1:c.1088_1102del

NM_000277.3:c.1088_1102del

NM_001354304.2:c.1088_1102del

Likely Pathogenic

PP4 PM2 PM3 PM4

PM1

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1092_1106del (p.Leu365_Leu369del) variant in PAH has been reported in 1 individual with PKU (PP4; PMID: 1363837) in trans with pathogenic variant p.R408W (PM3). This variant is absent in population databases (PM2). This variant is a 15 bp in-frame deletion in exon 11 (PM4). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3, PM4.

PP4

15 bp in-frame deletion in exon 11 of the phenylalanine hydroxylase (PAH) gene in a Polish patient with typical PKU. Plasma phenylalanine levels over 1.2 mM on both neonatal screening and revaluation at one month of age. PMID:1363837

In this study, we report on a 15 bp in-frame deletion in exon 11 of the phenylalanine hydroxylase (PAH) gene in a Polish patient with typical PKU. He had i) plasma phenylalanine levels over 1.2 mM on both neonatal screening and revaluation at one month of age, ii) dietary tolerance for phenylalanine of approximately 250 mg per day. He met therefore the clinical criteria for typical PKU. PubMed:1363837

PM2

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

PM3

detected in trans with R408W (pathogenic)

Digestion of genomic DNA using restriction enzyme Hindlll produced an abnormal pattern of hybridization consisting of a 7.5 kb abnormal band with the reduction in the intensity of a 5.0 kb invariant fragment in both the proband and his mother (Figure 1). the other mutant allele bore the R408W mutation. PubMed:1363837

PM4

Protein length changes as a result of in-frame deletion in a non-repeat region

PM1

34 pathogenic or likely pathogenic variants were found in a 134bp region surrounding this variant in exon 11 within the region 103237423-103237557 without any missense benign variants. Occurs in the catalytic domain (residues 143–410).

Occurs in the catalytic domain (residues 143–410). PubMed:18538294

Curation History

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