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]

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Variant: NM_000277.2(PAH):c.827T>A (p.Met276Lys)

CA229795

102857 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b816d0d3-13ff-424f-a001-bf9ec73622e4

HGVS expressions

NM_000277.2:c.827T>A

NM_000277.2(PAH):c.827T>A (p.Met276Lys)

NC_000012.12:g.102852830A>T

CM000674.2:g.102852830A>T

NC_000012.11:g.103246608A>T

CM000674.1:g.103246608A>T

NC_000012.10:g.101770738A>T

NG_008690.1:g.69773T>A

NG_008690.2:g.110581T>A

NM_000277.1:c.827T>A

NM_001354304.1:c.827T>A

NM_000277.3:c.827T>A

ENST00000307000.7:c.812T>A

ENST00000549247.6:n.586T>A

ENST00000553106.5:c.827T>A

Likely Pathogenic

PP4_Moderate PM2 PM3 PM5

PP3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.827T>A (p.Met276Lys) variant in PAH is absent from population databases, and found in the same codon as a previously reported pathogenic variant (p.Met276Val). It has been identified in trans with a known pathogenic variant (I95del), in which a defect of BH4 metabolism was excluded as a cause of elevated phenylalanine (PMID: 25894915).

PP4_Moderate

BH4 defect excluded in all patients PMID: 25894915

Variant in trans with a variant reported as pathogenic in clinvar (I95del). Single patient with MHP (Phe 278umol/L) PubMed:25894915

PM2

Absent from population databases

PM3

in trans with I95del (pathogenic in clinvar )(Chen, 2015)

single patient in trans with I95del (pathogenic in clinvar) PubMed:25894915

PM5

p.Met276Val is LP

PP3

SIFT = tolerated Provean = damaging REVEL = 0.783

Approved on: 2018-12-09

Published on: 2019-04-05

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