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_000277.1(PAH):c.728G>T (p.Arg243Leu)

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CA229719

102808 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3baf9d92-6ef7-42d6-96e7-f80bec7da14a

Approved on: 2021-02-14

Published on: 2021-06-09

HGVS expressions

NM_000277.1:c.728G>T

NM_000277.1(PAH):c.728G>T (p.Arg243Leu)

ENST00000553106.6:c.728G>T

ENST00000307000.7:c.713G>T

ENST00000549247.6:n.487G>T

ENST00000553106.5:c.728G>T

NM_000277.2:c.728G>T

NM_001354304.1:c.728G>T

NM_000277.3:c.728G>T

NM_001354304.2:c.728G>T

NC_000012.12:g.102852929C>A

CM000674.2:g.102852929C>A

NC_000012.11:g.103246707C>A

CM000674.1:g.103246707C>A

NC_000012.10:g.101770837C>A

NG_008690.1:g.69674G>T

NG_008690.2:g.110482G>T

Likely Pathogenic

PM5 PM2 PP4 PP3 PM3_Supporting

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.728G>T (p.Arg243Leu) variant in PAH has been reported in 1 individual with PKU detected with pathogenic variant p.R261Q (P 9 submitters) PMID: 12655553, 20217238. This variant is absent in population databases. Computational evidence supports a deleterious effect. Another missense change at the same amino acid,p .Arg243Gln, is pathogenic in ClinVar by multiple submitters (variation ID 591). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3, PM5, PP3.

PM5

p.Arg243Gln pathogenic 10 submitters

PM2

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

PP4

PMID 12655553: In footnote of Table 1. listed in one allele in a cohort of Germany PKU/MHP patients.

In footnote of Table 1. listed in one allele in a cohort of Germany PKU/MHP patients. PubMed:12655553

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster, REVEL=0.966

PM3_Supporting

detected with p.R261Q (P 9 submitters) PMID: 20217238 parental analysis not reported

Curation History

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