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.910C>T (p.Gln304Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16020892

558132 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 816effa6-e11c-4683-8d05-52c7dc2900e9

Approved on: 2023-10-15

Published on: 2023-10-15

HGVS expressions

NM_000277.2:c.910C>T

NM_000277.2(PAH):c.910C>T (p.Gln304Ter)

NC_000012.12:g.102851689G>A

CM000674.2:g.102851689G>A

NC_000012.11:g.103245467G>A

CM000674.1:g.103245467G>A

NC_000012.10:g.101769597G>A

NG_008690.1:g.70914C>T

NG_008690.2:g.111722C>T

ENST00000553106.6:c.910C>T

ENST00000307000.7:c.895C>T

ENST00000549247.6:n.669C>T

ENST00000551114.2:n.572C>T

ENST00000553106.5:c.910C>T

ENST00000635477.1:c.71C>T

NM_000277.1:c.910C>T

NM_001354304.1:c.910C>T

NM_000277.3:c.910C>T

NM_001354304.2:c.910C>T

NM_000277.3(PAH):c.910C>T (p.Gln304Ter)

Pathogenic

PP4 PVS1 PM2_Supporting

PM3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.910C>T (p.Gln304Ter) variant in PAH has been reported in at least 1 individual with PKU however without indication of the genotype (BH4 deficiency not ruled out) (PMID: 23357515) . This variant occurs in exon 8 of 13 of PAH, a gene where loss of function is a known disease mechanism, and is predicted to result in a truncated protein (with truncation of >10% of the encoded protein) or mRNA subject to nonsense-mediated decay. The c.910C>T variant is absent from gnomAD and the ESP population databases. Based on available information, this variant is considered to be pathogenic. PAH-specific ACMG/AMP criteria applied: PVS1, PM2_supporting, PP4.

PP4

detected on 1 allele in Czech HPA patient cohort (Phe > 120 μmol/L), BH4 deficiency not ruled out PMID: 23357515.

PVS1

Nonsense mutation in exon 8/13

PM2_Supporting

absent from gnomAD v2.1.1

PM3

Reported in 1 patient without genotype information.

Curation History

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