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.58C>T (p.Gln20Ter)

CA229635

102744 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0c208e34-37bd-4393-b238-7aeb88c8431e

HGVS expressions

NM_000277.2:c.58C>T

NM_000277.2(PAH):c.58C>T (p.Gln20Ter)

NC_000012.12:g.102917073G>A

CM000674.2:g.102917073G>A

NC_000012.11:g.103310851G>A

CM000674.1:g.103310851G>A

NC_000012.10:g.101834981G>A

NG_008690.1:g.5530C>T

NG_008690.2:g.46338C>T

NM_000277.1:c.58C>T

NM_001354304.1:c.58C>T

NM_000277.3:c.58C>T

ENST00000307000.7:c.-90C>T

ENST00000546844.1:c.58C>T

ENST00000547319.1:n.369C>T

ENST00000549111.5:n.154C>T

ENST00000550978.6:n.42C>T

ENST00000551337.5:c.58C>T

ENST00000551988.5:n.147C>T

ENST00000553106.5:c.58C>T

ENST00000635500.1:n.29-4175C>T

Pathogenic

PVS1 PP4 PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

Pathogenic: The c.58C>T (p.Gln20Ter) is a null variant reported in one patient with classic PKU phenotype (PVS1, PP4, PMID: 9391881). This variant is absent from population databases, including gnomAD, 1000 Genomes, and ESP (PM2). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.

PVS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP4

This variant was reported in a cohort patients with classic PKU classified on the basis of plasma phenylalanine concentration above 20mg/100mL. PMID: 9391881

This variant was reported in a cohort of 133 patients with classic PKU phenotype classified on the basis of plasma phenylalanine concentration above 20mg/100mL. One allele was detected (see Table 1) without further information on patient's genotype. PubMed:9391881

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2019-02-26

Published on: 2019-04-06

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