The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_000277.1(PAH):c.1097C>A (p.Pro366His)

CA229341

102521 (ClinVar)

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
UUID: 6adfe34f-36c9-4d33-b7e9-1fb4efef4726
Approved on: 2020-08-14
Published on: 2021-07-09

HGVS expressions

NM_000277.1:c.1097C>A
NM_000277.1(PAH):c.1097C>A (p.Pro366His)
ENST00000553106.6:c.1097C>A
ENST00000307000.7:c.1082C>A
ENST00000549247.6:n.856C>A
ENST00000551114.2:n.759C>A
ENST00000553106.5:c.1097C>A
ENST00000635477.1:n.201C>A
ENST00000635528.1:n.612C>A
NM_000277.2:c.1097C>A
NM_001354304.1:c.1097C>A
NM_000277.3:c.1097C>A
NM_001354304.2:c.1097C>A
NC_000012.12:g.102843748G>T
CM000674.2:g.102843748G>T
NC_000012.11:g.103237526G>T
CM000674.1:g.103237526G>T
NC_000012.10:g.101761656G>T
NG_008690.1:g.78855C>A
NG_008690.2:g.119663C>A
More

Likely Pathogenic

Met criteria codes 4
PM3_Strong PP4_Moderate PP3 PM2
Not Met criteria codes 1
PM5

Evidence Links 4

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
The c.1097C>A (p.Pro366His) variant in PAH has been reported in multiple individuals with PAH deficiency (BH4 deficiency excluded, PMID: 8268925). This variant is absent in population databases. This variant was detected with multiple pathogenic variants: p.R158Q (PMID: 8830172); c.165delT (p.F55fs, PMID: 19292873); c.1066-11G>A (PMID: 22841515); p.P281L (PMID: 21147011). Computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3_strong, PP3.
Met criteria codes
PM3_Strong
Seen in 3 PKU patients with known pathogenic mutations: R158Q (parental testing not reported, PMID: 8830172; c.165delT (p.F55fs). Parental analysis not reported PMID: 19292873; c.1066-11G>A parental analysis not reported; PMID: 22841515; P281L parental analysis not reported PMID: 21147011

PP4_Moderate
P366H seen on 1 PKU allele. Other potential causes of hyperphenylalaninemia had been ruled out (normal serum tyrosine, normal urinary excresion of biopterin and neopterin, and no indication of acquired hyperphenylalaninemia). PMID: 8268925

PP3
Predicted deleterious in SIFT, Polyphen2, MutationTaster. REVEL=0.929
PM2
Absent from controls in ExAC, gnomAD, 1000G, ESP
Not Met criteria codes
PM5
This variant is the only variant found in this codon in ClinVar.
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.