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_000277.3(PAH):c.1264G>A (p.Glu422Lys)

CA229422

102583 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 08baac31-a6cc-4e90-ba87-c22d0a4e1b44

Approved on: 2020-03-27

Published on: 2020-03-27

HGVS expressions

NM_000277.3:c.1264G>A

NM_000277.3(PAH):c.1264G>A (p.Glu422Lys)

NC_000012.12:g.102840451C>T

CM000674.2:g.102840451C>T

NC_000012.11:g.103234229C>T

CM000674.1:g.103234229C>T

NC_000012.10:g.101758359C>T

NG_008690.1:g.82152G>A

NG_008690.2:g.122960G>A

NM_000277.1:c.1264G>A

NM_000277.2:c.1264G>A

NM_001354304.1:c.1264G>A

NM_001354304.2:c.1264G>A

ENST00000307000.7:c.1249G>A

ENST00000551114.2:n.926G>A

ENST00000553106.5:c.1264G>A

ENST00000635477.1:n.368G>A

ENST00000635528.1:n.779G>A

Uncertain Significance

PP3 PM2 PP4_Moderate

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1264G>A (p.Glu422Lys) variant in PAH has been reported in 1 individual with PKU (BH4 deficiency excluded; PP4_Moderate; PMID: 31737040). This variant is absent from population databases (PM2). This variant is predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.96 (PP3). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PP3.

PP3

Predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.96.

PM2

Variant absent from population databases

PP4_Moderate

PMID: 31737040 - p.E44K detected in 1 patient via NGS with Phenylketonuria, Phe > 360umol/L, BH4 Deficiency excluded

PubMed:10541324

PubMed:31737040

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