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.355C>T (p.Pro119Ser)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA220582

92741 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 38a183ee-7e53-4c24-a250-50958f390c78

Approved on: 2018-07-29

Published on: 2019-04-06

HGVS expressions

NM_000277.2:c.355C>T

NM_000277.2(PAH):c.355C>T (p.Pro119Ser)

NC_000012.12:g.102877548G>A

CM000674.2:g.102877548G>A

NC_000012.11:g.103271326G>A

CM000674.1:g.103271326G>A

NC_000012.10:g.101795456G>A

NG_008690.1:g.45055C>T

NG_008690.2:g.85863C>T

NM_000277.1:c.355C>T

NM_001354304.1:c.355C>T

NM_000277.3:c.355C>T

ENST00000307000.7:c.340C>T

ENST00000549111.5:n.451C>T

ENST00000550978.6:n.339C>T

ENST00000551337.5:c.355C>T

ENST00000551988.5:n.444C>T

ENST00000553106.5:c.355C>T

Likely Pathogenic

PP3 PM3_Strong PP4_Moderate

PM2

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: PP3: in silico analysis supportive of damaging effect; PM3_Strong: In trans with R261Q (PMID 21147011), and in trans with IVS2+1G>A (PMID 12655554) (PMID:21147011; PMID:12655554); PP4_Moderate: BH4 deficiency excluded (PMID:21147011). In summary this variant meets criteria to be classified as likely pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PP3, PM3_Strong, PP4_Moderate).

PP3

in silico analysis supportive of damaging effect

PM3_Strong

In trans with R261Q (PMID 21147011), and in trans with IVS2+1G>A (PMID 12655554)

in trans with IVS2+1G>A PubMed:12655554

in trans with R261Q PubMed:21147011

PP4_Moderate

BH4 deficiency excluded

BH4 defect excluded at NBS and by sequencing of BH4 associated genes PubMed:21147011

PM2

PAH specific specifications state PM2 criteria as 0.02% (AF=0.0002)

Curation History

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