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.637C>T (p.Leu213Phe)

CA386296662

430401 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 9e5c49a1-c697-435f-872c-51c0b9ed23b6

Approved on: 2019-09-27

Published on: 2019-09-29

HGVS expressions

NM_000277.2:c.637C>T

NM_000277.2(PAH):c.637C>T (p.Leu213Phe)

NC_000012.12:g.102855205G>A

CM000674.2:g.102855205G>A

NC_000012.11:g.103248983G>A

CM000674.1:g.103248983G>A

NC_000012.10:g.101773113G>A

NG_008690.1:g.67398C>T

NG_008690.2:g.108206C>T

NM_000277.1:c.637C>T

NM_001354304.1:c.637C>T

NM_000277.3:c.637C>T

ENST00000307000.7:c.622C>T

ENST00000549111.5:n.733C>T

ENST00000553106.5:c.637C>T

Uncertain Significance

PP3 PM2 PM5

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.637C>T (p.Leu213Phe) variant in PAH is the same amino acid change as an established pathogenic variant, c.638T>C (p.Leu213Pro) VarID:92747. (PM5). This variant is absent in population databases (PM2). This variant has not been reported in the literature to our knowledge. Multiple lines of computational evidence support a deleterious effect (PP3). In summary, this variant meets criteria to be classified as uncertain significance for PAH.

PP3

Multiple lines of computational evidence support a deleterious effect (SIFT, D; PolyPhen2, D; MutationTaster, D; REVEL=0.912.

PM2

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

PM5

c.638T>C (p.Leu213Pro) is a known pathogenic variant (VarID:92747)

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