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.368G>T (p.Arg123Ile)

CA286501

102658 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 39d9d335-9484-430d-ab6e-318f3eef65d4

HGVS expressions

NM_000277.2:c.368G>T

NM_000277.2(PAH):c.368G>T (p.Arg123Ile)

NC_000012.12:g.102877535C>A

CM000674.2:g.102877535C>A

NC_000012.11:g.103271313C>A

CM000674.1:g.103271313C>A

NC_000012.10:g.101795443C>A

NG_008690.1:g.45068G>T

NG_008690.2:g.85876G>T

NM_000277.1:c.368G>T

NM_001354304.1:c.368G>T

NM_000277.3:c.368G>T

ENST00000307000.7:c.353G>T

ENST00000549111.5:n.464G>T

ENST00000550978.6:n.352G>T

ENST00000551337.5:c.368G>T

ENST00000551988.5:n.457G>T

ENST00000553106.5:c.368G>T

Uncertain Significance

PM2 PP3

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.368G>T (p.Arg123Ile) variant in PAH has not been reported in the literature to our knowledge. A reference listed in BioPKU/PAHdb cannot be located (Carducci, C 2009). This variant is absent from ExAC, gnomAD, 1000G, and ESP. Deleterious effect is predicted in SIFT, Polyphen2, MutationTaster. REVEL=0.864. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3.

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PP3

Deleterious effect predicted in SIFT, Polyphen2, MutationTaster. REVEL=0.864.

PM5

only variant found in this codon in ClinVar

Approved on: 2018-12-10

Published on: 2019-04-06

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