Evidence Repository
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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  • No ClinVar Id was directly found from the curated document
  • See Evidence submitted by expert panel for details.

Variant: NM_000277.1:c.835_836delinsTG

CA645372267

Gene: PAH
Condition: phenylketonuria
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: a3e440b0-140d-43fb-9d30-ac885cc5f588

HGVS expressions

NM_000277.1:c.835_836delinsTG
NC_000012.12:g.102852821_102852822delinsCA
CM000674.2:g.102852821_102852822delinsCA
NC_000012.11:g.103246599_103246600delinsCA
CM000674.1:g.103246599_103246600delinsCA
NC_000012.10:g.101770729_101770730delinsCA
NG_008690.1:g.69781_69782delinsTG
NG_008690.2:g.110589_110590delinsTG
ENST00000553106.6:c.835_836delinsTG
ENST00000307000.7:c.820_821delinsTG
ENST00000549247.6:n.594_595delinsTG
ENST00000553106.5:c.835_836delinsTG
NM_000277.2:c.835_836delinsTG
NM_001354304.1:c.835_836delinsTG
NM_000277.3:c.835_836delinsTG
NM_001354304.2:c.835_836delinsTG

Likely Pathogenic

Met criteria codes 4
PP3 PP4_Moderate PM3_Supporting PM2
Not Met criteria codes 1
PM5

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Phenylketonuria VCEP
The c.835_836delinsTG (p.Pro279Cys) variant in PAH has been reported in 1 individual with hyperphenylalaninemia (BH4 deficiency excluded), detected with pathogenic variant p.R408W (PMID: 21147011). This variant is absent in population databases. Computational evidence supports 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_supporting, PP3.
Met criteria codes
PP3
Deleterious effect predicted in SIFT, Polyphen2, MutationTaster
PP4_Moderate
P279C seen in 1 patient with hyperphenylalaninemia. BH4 deficiency excluded by assessment of the PAH gene and genes of the BH4 synthesis/recycling pathways (PTS and QDPR). PMID: 21147011
588 hyperphenylalaninemic patients were investigated. Assessment included PAH gene and genes of the BH4 synthesis/recycling pathways (PTS and QDPR). P279C seen on 1 allele. PubMed:21147011
PM3_Supporting
Seen with R408W in 1 patient. Parental testing not reported. PMID: 21147011
P279C seen with R408W (VarID 577, Pathogenic in ClinVar) in 1 patient PubMed:21147011
PM2
Absent from ExAC, 1000G, ESP, gnomAD
Not Met criteria codes
PM5
P279L and P279A are likely pathogenic in ClinVar
Approved on: 2020-11-13
Published on: 2022-03-11
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